Mesenchymal stem/stromal cell-based therapies for severe viral pneumonia: therapeutic potential and challenges.

Severe viral pneumonia is a significant cause of morbidity and mortality globally, whether due to outbreaks of endemic viruses, periodic viral epidemics, or the rarer but devastating global viral pandemics. While limited anti-viral therapies exist, there is a paucity of direct therapies to directly attenuate viral pneumonia-induced lung injury, and management therefore remains largely supportive. Mesenchymal stromal/stem cells (MSCs) are receiving considerable attention as a cytotherapeutic for viral pneumonia. Several properties of MSCs position them as a promising therapeutic strategy for viral pneumonia-induced lung injury as demonstrated in pre-clinical studies in relevant models. More recently, early phase clinical studies have demonstrated a reassuring safety profile of these cells. These investigations have taken on an added importance and urgency during the COVID-19 pandemic, with multiple trials in progress across the globe. In parallel with clinical translation, strategies are being investigated to enhance the therapeutic potential of these cells in vivo, with different MSC tissue sources, specific cellular products including cell-free options, and strategies to 'licence' or 'pre-activate' these cells, all being explored. This review will assess the therapeutic potential of MSC-based therapies for severe viral pneumonia. It will describe the aetiology and epidemiology of severe viral pneumonia, describe current therapeutic approaches, and examine the data suggesting therapeutic potential of MSCs for severe viral pneumonia in pre-clinical and clinical studies. The challenges and opportunities for MSC-based therapies will then be considered.

Global maps of travel time to healthcare facilities.

Access to healthcare is a requirement for human well-being that is constrained, in part, by the allocation of healthcare resources relative to the geographically dispersed human population1-3. Quantifying access to care globally is challenging due to the absence of a comprehensive database of healthcare facilities. We harness major data collection efforts underway by OpenStreetMap, Google Maps and academic researchers to compile the most complete collection of facility locations to date. Leveraging the geographically variable strengths of our facility datasets, we use an established methodology4 to characterize travel time to healthcare facilities in unprecedented detail. We produce maps of travel time with and without access to motorized transport, thus characterizing travel time to healthcare for populations distributed across the wealth spectrum. We find that just 8.9% of the global population (646 million people) cannot reach healthcare within one hour if they have access to motorized transport, and that 43.3% (3.16 billion people) cannot reach a healthcare facility by foot within one hour. Our maps highlight an additional vulnerability faced by poorer individuals in remote areas and can help to estimate whether individuals will seek healthcare when it is needed, as well as providing an evidence base for efficiently distributing limited healthcare and transportation resources to underserved populations both now and in the future.

Travel time to health facilities in areas of outbreak potential: maps for guiding local preparedness and response.

BACKGROUND: Repeated outbreaks of emerging pathogens underscore the need for preparedness plans to prevent, detect, and respond. As countries develop and improve National Action Plans for Health Security, addressing subnational variation in preparedness is increasingly important. One facet of preparedness and mitigating disease transmission is health facility accessibility, linking infected persons with health systems and vice versa. Where potential patients can access care, local facilities must ensure they can appropriately diagnose, treat, and contain disease spread to prevent secondary transmission; where patients cannot readily access facilities, alternate plans must be developed. Here, we use travel time to link facilities and populations at risk of viral hemorrhagic fevers (VHFs) and identify spatial variation in these respective preparedness demands. METHODS AND FINDINGS: We used geospatial resources of travel friction, pathogen environmental suitability, and health facilities to determine facility accessibility of any at-risk location within a country. We considered in-country and cross-border movements of exposed populations and highlighted vulnerable populations where current facilities are inaccessible and new infrastructure would reduce travel times. We developed profiles for 43 African countries. Resulting maps demonstrate gaps in health facility accessibility and highlight facilities closest to areas at risk for VHF spillover. For instance, in the Central African Republic, we identified travel times of over 24 h to access a health facility. Some countries had more uniformly short travel times, such as Nigeria, although regional disparities exist. For some populations, including many in Botswana, access to areas at risk for VHF nationally was low but proximity to suitable spillover areas in bordering countries was high. Additional analyses provide insights for considering future resource allocation. We provide a contemporary use case for these analyses for the ongoing Ebola outbreak. CONCLUSIONS: These maps demonstrate the use of geospatial analytics for subnational preparedness, identifying facilities close to at-risk populations for prioritizing readiness to detect, treat, and respond to cases and highlighting where gaps in health facility accessibility exist. We identified cross-border threats for VHF exposure and demonstrate an opportunity to improve preparedness activities through the use of precision public health methods and data-driven insights for resource allocation as part of a country's preparedness plans.

Genomic and epidemiological monitoring of yellow fever virus transmission potential.

The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.

A global map of travel time to cities to assess inequalities in accessibility in 2015.

The economic and man-made resources that sustain human wellbeing are not distributed evenly across the world, but are instead heavily concentrated in cities. Poor access to opportunities and services offered by urban centres (a function of distance, transport infrastructure, and the spatial distribution of cities) is a major barrier to improved livelihoods and overall development. Advancing accessibility worldwide underpins the equity agenda of 'leaving no one behind' established by the Sustainable Development Goals of the United Nations. This has renewed international efforts to accurately measure accessibility and generate a metric that can inform the design and implementation of development policies. The only previous attempt to reliably map accessibility worldwide, which was published nearly a decade ago, predated the baseline for the Sustainable Development Goals and excluded the recent expansion in infrastructure networks, particularly in lower-resource settings. In parallel, new data sources provided by Open Street Map and Google now capture transportation networks with unprecedented detail and precision. Here we develop and validate a map that quantifies travel time to cities for 2015 at a spatial resolution of approximately one by one kilometre by integrating ten global-scale surfaces that characterize factors affecting human movement rates and 13,840 high-density urban centres within an established geospatial-modelling framework. Our results highlight disparities in accessibility relative to wealth as 50.9% of individuals living in low-income settings (concentrated in sub-Saharan Africa) reside within an hour of a city compared to 90.7% of individuals in high-income settings. By further triangulating this map against socioeconomic datasets, we demonstrate how access to urban centres stratifies the economic, educational, and health status of humanity.

The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015.

Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.

Antitumor effects of TRAIL-expressing mesenchymal stromal cells in a mouse xenograft model of human mesothelioma.

Malignant mesothelioma (MM) remains a highly deadly malignancy with poor treatment option. The MM cells further promote a highly inflammatory microenvironment, which contributes to tumor initiation, development, severity and propagation. We reasoned that the anti-inflammatory actions of mesenchymal stromal cells (MSCs) and further antitumor effects of MSCs engineered to overexpress tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein (MSC-TRAIL) would effectively inhibit mesothelioma growth. Using a mouse xenograft model of intraperitoneal human mesothelioma, native mouse (mMSCs) or human (hMSC) MSCs were administered either systemically (intravenously or intraperitoneally) at various times following tumor inoculation. Both mMSCs and hMSCs localized at the sites of MM tumor growth in vivo and decreased local inflammation. Further, a trend towards decrease in tumor burden was observed. Parallel studies of in vitro exposure of nine primary human mesothelioma cell lines to mMSCs or hMSCs demonstrated reduced tumor cell migration. MSC-TRAIL exposure induced apoptosis of TRAIL-sensitive MM cells in vitro, and both mouse and human MSC-TRAIL significantly reduced the inflammatory tumor environment in vivo. Moreover, human MSC-TRAIL administration significantly reduced peritoneal tumor burden in vivo and increased tumor cell apoptosis. These proof-of-concept studies suggest that TRAIL-expressing MSCs may be useful against malignant mesothelioma.

High precision isotope measurements reveal poor control of copper metabolism in parkinsonism.

Disordered copper metabolism may be important in the aetiology of Parkinsonism, as caeruloplasmin is a key enzyme in handling oxidative stress and is involved in the synthesis pathway of dopamine. The human Cu metabolism of ten Parkinsonism patients was compared to ten healthy controls with the aid of a stable (65)Cu isotope tracer. The analyses of blood serum (65)Cu/(63)Cu ratios yielded individual isotopic profiles, which indicate that the Cu metabolism is less controlled in patients with Parkinsonism. Modelling based on both isotope tracer and total Cu concentrations suggests that 30% of the subjects affected by Parkinsonism have abnormally large Cu stores in tissues. To detect the small differences in Cu metabolism between Parkinsonism and controls, the analysis of stable isotope composition must be performed using multiple-collector inductively coupled plasma mass spectrometry and the associated sample preparation techniques. This pilot investigation supports full-scale medical studies into the Cu metabolism of those with Parkinsonism.

Stable isotopes of Cu and Zn in higher plants: evidence for Cu reduction at the root surface and two conceptual models for isotopic fractionation processes.

Recent reports suggest that significant fractionation of stable metal isotopes occurs during biogeochemical cycling and that the uptake into higher plants is an important process. To test isotopic fractionation of copper (Cu) and zinc (Zn) during plant uptake and constrain its controls, we grew lettuce, tomato, rice and durum wheat under controlled conditions in nutrient solutions with variable metal speciation and iron (Fe) supply. The results show that the fractionation patterns of these two micronutrients are decoupled during the transport from nutrient solution to root. In roots, we found an enrichment of the heavier isotopes for Zn, in agreement with previous studies, but an enrichment of isotopically light Cu, suggesting a reduction of Cu(II) possibly at the surfaces of the root cell plasma membranes. This observation holds for both graminaceous and nongraminaceaous species and confirms that reduction is a predominant and ubiquitous mechanism for the acquisition of Cu into plants similar to the mechanism for the acquisition of iron (Fe) by the strategy I plant species. We propose two preliminary models of isotope fractionation processes of Cu and Zn in plants with different uptake strategies.

Reduced incidence and severity of experimental autoimmune arthritis in mice expressing catalytically inactive A disintegrin and metalloproteinase 8 (ADAM8).

A disintegrin and metalloproteinase 8 (ADAM8), a catalytically active member of the ADAMs family of enzymes, is expressed primarily on immune cells and thus probably involved in inflammatory responses. ADAM8 is also produced by chondrocytes, and recombinant ADAM8 can induce cartilage catabolism. We therefore decided to test the role of ADAM8 in autoimmune inflammatory arthritis using transgenic mice expressing catalytically inactive ADAM8. Transgenic DBA/1J mice expressing an inactivating point mutation in the ADAM8 gene to change Glu330 to Gln330 (ADAM8(EQ)) were generated to evaluate the proteolytic function of ADAM8 in an lipopolysaccharide-synchronized collagen-induced arthritis (LPS-CIA) model of autoimmune arthritis. The systemic inflammatory reaction to LPS was also evaluated in these mice. Expression profiling of paw joints from wild-type mice revealed that ADAM8 mRNA levels increased at the onset of clinical arthritis and correlated well with cellular macrophage markers. When subjected to LPS-CIA, ADAM8(EQ) mice demonstrated decreased incidence and severity of clinical arthritis compared to wild-type mice. Histological examination of paw joints from ADAM8(EQ) mice confirmed marked attenuation of synovial inflammation, cartilage degradation and bone resorption when compared to wild-type mice. However, transgenic mice and wild-type mice responded similarly to LPS-induced systemic inflammation with regard to mortality, organ weights, neutrophil sequestration and serum cytokine/chemokine production. We conclude that ADAM8 proteolytic activity plays a key role in the development of experimental arthritis and may thus be an attractive target for the treatment of arthritic disorders while minimizing risk of immunocompromise.

Stable lead isotope compositions in selected coals from around the world and implications for present day aerosol source tracing.

The phasing out of leaded gasoline in many countries around the world at the end of the last millennium has resulted in a complex mixture of lead sources in the atmosphere. Recent studies suggest that coal combustion has become an important source of Pb in aerosols in urban and remote areas. Here, we report lead concentration and isotopic composition for 59 coal samples representing major coal deposits worldwide in an attempt to characterize this potential source. The average concentration in these coals is 35 microg Pb g(-1), with the highest values in coals from Spain and Peru and the lowest in coals from Australia and North America. The 206Pb/207Pb isotope ratios range between 1.15 and 1.24, with less radiogenic Pb in coals from Europe and Asia compared to South and North America. Comparing the Pb isotopic signatures of coals from this and previous studies with those published for Northern and Southern Hemisphere aerosols, we hypothesize that coal combustion might now be an important Pb source in China, the eastern U.S., and to some extent, in Europe but not as yet in other regions including South Africa, South America, and western U.S. This supports the notion that "old Pb pollution" from leaded gasoline reemitted into the atmosphere or long-range transport (i.e., from China to the western U.S.) is important. Comparing the isotope ratios of the coals, the age of the deposits, and Pb isotope evolution models for the major geochemical reservoirs suggests that the PbIC in coals is strongly influenced by the depositional coal forming environment.

Review paper: modulation of mononuclear phagocyte function by Mycobacterium avium subsp. paratuberculosis.

Pathogenic mycobacteria are highly adapted for survival within host mononuclear phagocytes. This is largely due to the organism's capacity to prevent macrophage activation, block phagosome acidification and maturation, and attenuate presentation of antigens to the immune system. Mycobacterium avium subsp. paratuberculosis (MAP) is one such organism that modulates the ruminant innate immune response. It is the causative agent in paratuberculosis, a chronic progressive granulomatous enteritis in ruminants. MAP initially interacts with cell membrane receptors on bovine mononuclear phagocytes and initiates cell signaling responses and phagocytosis. Mannosylated liparabinomannan (Man-LAM) is a major component of the MAP cell wall that interacts with the cell membrane of mononuclear phagocytes and may be a major virulence factor. Toll-like receptor 2 (TLR2) has been incriminated as major signaling receptor that binds to MAP and initiates signaling though the mitogen-activated protein kinase (MAPK)-p38 pathway. This pathway induces transcription of interleukin (IL)-10. Early production of IL-10 suppresses proinflammatory cytokines, chemokines, IL-12, and major histocompatability factor class-II expression. Both IL-10 dependent and IL-10 independent mechanisms appear to be involved in attenuation of phagosome acidification and phagolysosome fusion. Many of the suppressive effects of MAP on bovine mononuclear phagocytes can be reproduced by exposure of bovine monocytes to Man-LAM. Therefore, MAP Man-LAM-induced TLR2-MAPK-p38 signaling with resultant excessive IL-10 expression has emerged as one of the mechanisms by which MAP organisms suppress inflammatory, immune, and antimicrobial responses and promote their survival within host mononuclear phagocytes.

Bone marrow pathology in dogs and cats with non-regenerative immune-mediated haemolytic anaemia and pure red cell aplasia.

Many dogs and cats with immune-mediated haemolytic anaemia (IMHA) lack a bone marrow erythroid regenerative response. To better understand the failure of the bone marrow to respond to the anaemia, bone marrow pathology associated with non-regenerative IMHA and pure red cell aplasia (PRCA) was reviewed. Eighty-two affected dogs and 57 affected cats were identified from a population presenting to a referral hospital over a 10-year period. Fifty-five dogs had non-regenerative IMHA (38 had bone marrow erythroid hyperplasia and 17 had erythroid maturation arrest) and 27 had pure red cell aplasia (PRCA). Twenty-eight cats had non-regenerative IMHA (24 had erythroid hyperplasia and 4 had erythroid maturation arrest) and 29 had PRCA. A variety of pathological changes were observed in bone marrow aspirates and core biopsy specimens taken from these animals. These changes included dysmyelopoiesis, myelonecrosis, myelofibrosis, interstitial oedema, haemorrhage, acute inflammation, haemophagocytic syndrome, lymphocyte aggregation, and lymphocyte or plasma cell hyperplasia. In both dogs and cats, dysmyelopoiesis, myelonecrosis, myelofibrosis, interstitial oedema, haemorrhage, acute inflammation and haemophagocytic syndrome were primarily noted in bone marrow specimens where there was evidence of erythroid hyperplasia. These animals were also more often neutropenic and thrombocytopenic, and had decreased 60 day survival when compared with dogs or cats with non-regenerative anaemia associated with erythroid maturation arrest or PRCA. Therefore, the pathogenesis of the non-regenerative anaemia in non-regenerative IMHA may involve both antibody-mediated destruction of bone marrow precursor cells and pathological events within the bone marrow that result in ineffective erythropoiesis.

Transcriptional profiling and pathway analysis of monosodium iodoacetate-induced experimental osteoarthritis in rats: relevance to human disease.

OBJECTIVE: The objective of this study was to characterize the rat monosodium iodoacetate (MIA)-induced model for osteoarthritis (OA) and determine the translatability of this model to human disease. This was accomplished through pathway, network and system level comparisons of transcriptional profiles generated from animal and human disease cartilage. METHODS: An OA phenotype was induced in rat femorotibial joints following a single injection of 200mug MIA per knee joint for a period of 2 or 4 weeks. Lesion formation in the rat joints was confirmed by histology. Gene expression changes were measured using the Agilent rat whole genome microarrays. Cartilage was harvested from human knees and gene expression changes were measured using the Agilent human arrays. RESULTS: One thousand nine hundred and forty-three oligos were differentially expressed in the MIA model, of these, approximately two-thirds were up-regulated. In contrast, of the 2130 differentially expressed oligos in human disease tissue, approximately two-thirds were down-regulated. This dramatic difference was observed throughout each level of the comparison. The total overlap of genes modulated in the same direction between rat and human was less than 4%. Matrix degradation and inflammatory genes were differentially regulated to a much greater extent in MIA than human disease tissue. CONCLUSION: This study demonstrated, through multiple levels of analysis, that little transcriptional similarity exists between rat MIA and human OA derived cartilage. As disease modulatory activities for potential therapeutic agents often do not translate from animal models to human disease, this and like studies may provide a basis for understanding the discrepancies.

A rapid and reliable method for Pb isotopic analysis of peat and lichens by laser ablation-quadrupole-inductively coupled plasma-mass spectrometry for biomonitoring and sample screening.

An analytical protocol for rapid and reliable laser ablation-quadrupole (LA-Q)- and multi-collector (MC-) inductively coupled plasma-mass spectrometry (ICP-MS) analysis of Pb isotope ratios ((207)Pb/(206)Pb and (208)Pb/(206)Pb) in peats and lichens is developed. This technique is applicable to source tracing atmospheric Pb deposition in biomonitoring studies and sample screening. Reference materials and environmental samples were dry ashed and pressed into pellets for introduction by laser ablation. No binder was used to reduce contamination. LA-MC-ICP-MS internal and external precisions were <1.1% and <0.3%, respectively, on both (207)Pb/(206)Pb and (208)Pb/(206)Pb ratios. LA-Q-ICP-MS internal precisions on (207)Pb/(206)Pb and (208)Pb/(206)Pb ratios were lower with values for the different sample sets <14.3% while external precisions were <2.9%. The level of external precision acquired in this study is high enough to distinguish between most modern Pb sources. LA-MC-ICP-MS measurements differed from thermal ionisation mass spectrometry (TIMS) values by 1% or less while the accuracy obtained using LA-Q-ICP-MS compared to solution MC-ICP-MS was 3.1% or better using a run bracketing (RB) mass bias correction method. Sample heterogeneity and detector switching when measuring (208)Pb by Q-ICP-MS are identified as sources of reduced analytical performance.

Mucosal immune response in cattle with subclinical Johne's disease.

Mycobacterium avium subsp. paratuberculosis is the causative agent of Johne's disease, a chronic granulomatous enteritis of wild and domestic ruminants. During a long subclinical period, the organism persists in the intestine despite systemic cellular and humoral immune responses. To explore the mucosal immune response in Johne's disease, we isolated mononuclear leukocytes from the ileum of cows naturally infected with M. avium subsp. paratuberculosis and from cows that were not infected. We evaluated the immunophenotype of these cells and the proliferative responses after the addition of M. avium subsp. paratuberculosis sonicate or B-cell or T-cell mitogens. Although the percentage of T cells was increased in infected cows, these cells consisted mostly of memory (CD2+CD62L-) and regulatory (CD4+CD25+) T cells. Further evidence of immune hyporesponsiveness included a decrease in the percentage of T cells with an activated phenotype and a decrease in cells expressing major histocompatibility factor class II (MHC class II). Unlike the spleen, ileal lymphocytes from infected cows failed to proliferate in response to M. avium subsp. paratuberculosis sonicate. Additionally, ileal lymphocytes from infected cows proliferated poorly in response to concanavalin A and pokeweed mitogen, suggesting generalized T cell and B cell hyporesponsiveness. These results indicate that a state of tolerance may exist in the intestine of cows subclinically infected with M. avium subsp. paratuberculosis organisms in subclinically infected cows. This effect may be induced, at least in part, by proliferation of regulatory T cells that nonspecifically suppress mucosal immune responsiveness.

Isotopic discrimination of zinc in higher plants.

* The extent of isotopic discrimination of transition metals in biological processes is poorly understood but potentially has important applications in plant and biogeochemical studies. * Using multicollector inductively coupled plasma (ICP) mass spectrometry, we measured isotopic fractionation of zinc (Zn) during uptake from nutrient solutions by rice (Oryza sativa), lettuce (Lactuca sativa) and tomato (Lycopersicon esculentum) plants. * For all three species, the roots showed a similar extent of heavy Zn enrichment relative to the nutrient solution, probably reflecting preferential adsorption on external root surfaces. By contrast, a plant-species specific enrichment of the light Zn isotope occurred in the shoots, indicative of a biological, membrane-transport controlled uptake into plant cells. The extent of the fractionation in the shoots further depended on the Zn speciation in the nutrient solution. * The observed isotopic depletion in heavy Zn from root to shoot (-0.13 to -0.26 per atomic mass unit) is equivalent to roughly a quarter of the total reported terrestrial variability of Zn isotopic compositions (c. 0.84 per atomic mass unit). Plant uptake therefore represents an important source of isotopic variation in biogeochemical cycling of Zn.

Gene expression and antimicrobial activity of bovine macrophages in response to Mycobacterium avium subsp. paratuberculosis.

We evaluated gene expression and antimicrobial responses of bovine monocyte-derived macrophages incubated with Mycobacterium avium subsp. paratuberculosis (M. a. ptb), the causative agent of Johne's disease. Gene expression was evaluated by the use of human noncompetitive high-density oligonucleotide microarrays. Bovine messenger RNA hybridized with 14.2-18.2% of the 12,600 oligonucleotide probe sets. When macrophages incubated with M. a. ptb were compared with nonactivated control macrophages, macrophages activated by addition of interferon-gamma and lipopolysaccharide, and macrophages incubated with Mycobacterium avium subspecies avium (M. a. a), 47, 79, and 27 genes, respectively, were differentially expressed. Differential expression of six of these genes was confirmed using reverse transcriptase polymerase chain reaction. Several functional assays were performed to evaluate the potential relevance of differentially expressed genes to host defense. Macrophages phagocytizing M. a. a had a greater capacity to kill the organisms and to acidify phagosomes and a greater degree of apoptosis than did macrophages incubated with M. a. ptb. The results of these studies indicate that multiple genes and metabolic pathways are differentially expressed by macrophages ingesting mycobacterial organisms. Although the intracellular fate of mycobacterial organisms appears to be dependent on a complex interaction between macrophage and organism, phagosome acidification and apoptosis may play central roles in organism survival.

Lead isotopes in lichen transplants around a Cu smelter in Russia determined by MC-ICP-MS reveal transient records of multiple sources.

Transplants of the lichen Hypogymnia physodes, which is relatively tolerant to SO2 and heavy metals, were deployed for 3 months over a 60 km long SW-NE transect centered on a highly polluting Cu smelter and its adjoining town of Karabash, southern Urals, Russia. The abundance of 206Pb, 207Pb, 208Pb, and 204Pb were determined by MC-ICP-MS. The measurement of 204Pb revealed critical features, which would otherwise remain concealed: (i) The precise isotope ratios referenced to 204Pb allowed several different sources to be resolved even within the small area covered: (a) the obvious pollutant source of the Karabash Cu smelter; (b) two dispersed sources, likely to include soil with lower and different contributions of thorogenic and uranogenic lead; and (c) one anthropogenic source with higher contribution of 235U derived Pb. (ii) In part of the transect, the Pb isotope composition changed while the Pb concentrations remained the same. This indicates that the Pb content of the transplantation material from the background site was largely replaced and that the transplants provide a transient record reflecting a continuous accumulation and loss of environmental Pb, probably mainly in the form of extracellular particles. Overall, the method of lichen transplantation coupled with Pb isotope ratio determinations proved effective in assessing the usefulness of lichens in biomonitoring and in resolving different sources of atmospheric deposition.