Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by ...single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.
•Biodynamic modelling is used to predict accumulation of Ag, As and Zn in S. plana.•Dissolved and sediment-associated metals contribute to total metal bioaccumulation.•Relative importance varies with ...water and sediment concentrations and geochemistries.
Biodynamic modelling was used to investigate the uptake and accumulation of three trace metals (Ag, As, Zn) by the deposit feeding estuarine bivalve mollusc Scrobicularia plana. Radioactive labelling techniques were used to quantify the rates of trace metal uptake (and subsequent elimination) from water and sediment diet. The uptake rate constant from solution (±SE) was greatest for Ag (3.954±0.375lg−1d−1) followed by As (0.807±0.129lg−1d−1) and Zn (0.103±0.016lg−1d−1). Assimilation efficiencies from ingested sediment were 40.2±1.3% (Ag), 31.7±1.0% (Zn) and 25.3±0.9% (As). Efflux rate constants after exposure to metals in the solution or sediment fell in the range of 0.014–0.060d−1. By incorporating these physiological parameters into biodynamic models, our results showed that dissolved metal is the predominant source of accumulated Ag, As and Zn in S. plana, accounting for 66–99%, 50–97% and 52–98% of total accumulation of Ag, As and Zn, respectively, under different field exposure conditions. In general, model-predicted steady state concentrations of Ag, As and Zn matched well with those observed in clams collected in SW England estuaries. Our findings highlight the potential of biodynamic modelling to predict Ag, As and Zn accumulation in S. plana, taking into account specific dissolved and sediment concentrations of the metals at a particular field site, together with local water and sediment geochemistries.
Arsenic bioaccumulation in the deposit-feeding polychaete
Arenicola marina has been investigated using biodynamic modelling. Radiotracer techniques were used to determine the rates of uptake of As as ...arsenate from water and sediment and its subsequent efflux in the laboratory. Lugworms accumulated As from solution linearly at concentrations of 2–20
μg
l
−1, with a corresponding uptake rate constant of 0.1648
±
0.0135
l
g
−1
d
−1. 7.8
±
0.8% (assimilation efficiency) of the As ingested bound to sediments was retained after egestion of unassimilated metal. Elimination of As followed a two-compartment model, with mean efflux rate constants (from the slow pool) very similar for As accumulated from solution and ingested sediments (0.0449
±
0.0034 and 0.0478
±
0.0225
d
−1, respectively) and a corresponding biological half-time of roughly 15
d. A biodynamic model was constructed and validated through the comparison of biodynamic model predictions against measured bioaccumulated concentrations in lugworms from five UK estuaries. The model accurately predicted bioaccumulated As concentrations in lugworms using mean values of relevant physiological parameters (uptake rate, efflux rate and growth rate constants), a site-specific ingestion rate (calculated according to mean worm size and sediment organic matter content and expressed as the rate of ingestion of the mass of fine sediment), a site-specific sediment concentration measured after HCl extraction, and a standard dissolved As concentration. This combination of parameters showed that sediment ingestion contributed 30–60% of the total As accumulated by lugworms at the studied sites, depending on the different geochemistry at each site. This study showed that it is difficult to predict accurately As bioaccumulation at sites with different chemistries, unless that chemistry is taken into account.
Many estuaries of southwest England were heavily contaminated with toxic metals associated with the mining of copper and other metals, particularly between 1850 and 1900. The question remains whether ...the passage of time has brought remediation to these estuaries. In 2003 and 2006 we revisited sites in 5 metal-contaminated estuaries sampled in the 1970s and 1980s — Restronguet Creek, Gannel, West Looe, East Looe and Tavy. We evaluate changes in metal contamination in sediments and in metal bioavailabilities in sediments and water to local organisms employed as biomonitors. We find that the decline in contamination in these estuaries is complex. Differences in bioavailable contamination in the water column were detectable, as were significant detectable changes in at least some estuaries in bioavailable metal contamination originating from sediments. However, in the 100years since mining activities declined, bioavailable contamination has not declined to the regional baseline in any estuary affected by the mine wastes. The greatest decline in contamination occurred in the one instance (East Looe) where a previous industrial source of (Ag) contamination was considered. We used the macroalgae Fucus vesiculosus and Ascophyllum nodosum as biomonitors of dissolved metal bioavailabilities and the deposit feeders Nereis diversicolor and Scrobicularia plana as biomonitors of bioavailable metal in sediments. We found no systematic decrease in the atypically high Ag, Cu, Pb and Zn concentrations in the estuarine sediments over a 26year period. Accumulated metal (Ag, As, Cu, Pb, and Zn) concentrations in the deposit feeders are similarly still atypically high in at least one estuary for each metal, and there is no consistent evidence for general decreases in sediment metal bioavailabilities over time. We conclude that the legacy of mining in sheltered estuaries of southwest England is the ongoing presence of sediments rich in metals bioavailable to deposit feeders, while dissolved metal bioavailabilities from this historical source alone are no longer atypically high.
► SW England estuaries are contaminated with toxic metals from historical mining. ► High metal concentrations remain in the sediments. ► High metal concentrations still in biomonitors of sediment contamination. ► Mining legacy is sediments rich in metals bioavailable to deposit feeders. ► Bioavailabilities of dissolved metals from historical mining are no longer high.
In an investigation of the trophic transfer of ecotoxicologically significant amounts of trace metals from prey to predator, Palaemonetes varians were fed with diets of Nereis diversicolor from two ...metal-contaminated estuaries, the Tavy and Restronguet Creek in SW England, and a control estuary, the Blackwater in SE England. The decapods accumulated increased concentrations of copper (but not zinc) from the metal-contaminated worms above an initial apparently regulated body copper concentration, in response to a high dietary copper input over a period up to 30days. High dietary challenges of copper caused the induction of MTLP (metallothionein-like proteins) in the hepatopancreas of the feeding decapods as a detoxification response, although the non-detoxified subcellular component of hepatopancreas accumulated copper also increased over time, probably in association with sublethal toxic effects.
•Field-contaminated prey provides a source of toxic metals to a predator.•A predator can take up ecotoxicologically significant amounts of copper from prey.•Dietary copper was taken up and detoxified by metallothionein-like proteins.•Some dietary copper accumulated was not detoxified and potentially toxic.
We test the hypothesis that accumulated metal in prey that is trophically available to one predator is not necessarily equally trophically available to another predator feeding on the same prey, ...given the variability between invertebrate digestive systems. We provided two predators, the neogastropod mollusc Hinia reticulata and the palaemonid decapod crustacean Palaemonetes varians, with the digestive glands and adductor muscles of four bivalves radiolabelled with Zn, Cd or Ag. The bivalves (the mussel Mytilus edulis, the clam Ruditapes philippinarum, the scallop Aequipecten opercularis, the oyster Crassostrea gigas) have different metal accumulation patterns with differential dependence on soluble and insoluble detoxification, as confirmed by fractionation of the prey tissues. We found no consistent significant difference between the AE of the two predators for the three trace metals accumulated in the same prey tissues. There were no significant correlations for either predator between percentages of metal in soluble form (or soluble form with organelle-associated metal) and percentage AE for any of the three metals, allowing the conclusion that both predators are assimilating each metal from more than the soluble and organelle-associated metal fractions. For neither predator did an increased percentage of Zn in the form of metal rich granules (MRG) affect its Zn AE, but increases in the percentages of both Cd and Ag bound to MRG decreased the AE of the relevant metal in P. varians but not H. reticulata. Thus the Cd and Ag in some Cd-rich and Ag-rich granules in the bivalve tissues are not as trophically available to P. varians as they are to H. reticulata. This interspecific difference confirms that the neogastropod has the stronger digestive and assimilative powers involving Cd and Ag bound in prey than the palaemonid decapod.
Radiotracer techniques were used to determine the rates of trace metal (Ag, Cd and Zn) uptake and elimination (33
psu, 10
°C) from water and sediment by the deposit-feeding polychaete
Arenicola ...marina, proposed as a test species for estuarine-marine sediments in whole-sediment toxicity tests. Metal uptake rates from solution increase with increasing dissolved metal concentrations, with uptake rate constants (±
SE) (l
g
−1
d
−1) of 1.21
±
0.11 (Ag), 0.026
±
0.002 (Zn) and 0.012
±
0.001 (Cd). Assimilation efficiencies from ingested sediments were measured using a pulse-chase radiotracer feeding technique in two different lugworm populations, one from a commercial supplier (Blyth, Northumberland, UK) and the other a field-collected population from the outer Thames estuary (UK). Assimilation efficiencies ranged from 2 to 20% for Zn, 1 to 6% for Cd and 1 to 9% for Ag for the Northumberland worms, and from 3 to 22% for Zn, 6 to 70% for Cd and 2 to 15% for Ag in the case of the Thames population. Elimination of accumulated metals followed a two-compartment model, with similar efflux rate constants for Zn and Ag and lower rates of elimination of Cd from the slow pool. Efflux rate constants (±
SE) of Zn and Ag accumulated from the dissolved phase were 0.037
±
0.002 and 0.033
±
0.006
d
−1 whereas Cd was eliminated with an efflux rate constant one order of magnitude lower (0.003
±
0.002
d
−1). When metals were accumulated from ingested sediments, the efflux rate constants for the slow-exchanging compartment were of the same order of magnitude for the three metals, and of the same order of magnitude as those derived after the dissolved exposure for Zn and Ag (0.042
±
0.004 and 0.056
±
0.012
d
−1 for Zn and 0.044
±
0.012 and 0.069
±
0.016
d
−1 for Ag for the Northumberland and Thames populations, respectively). Cd accumulated from ingested sediments was eliminated with a rate constant not different from the fast-exchanging compartment after the water-only exposure (0.025
±
0.012 and 0.020
±
0.004
d
−1 for the Northumberland and Thames populations, respectively). A biodynamic model was used to estimate the relative importance of the dissolved phase versus ingested sediment as source of metal for the worms, showing that more than 90% of the Zn and Cd and more than 70% of Ag in lugworms is accumulated from sediment ingestion at realistic environmental concentrations. The model also shows that metal accumulation is highly dependent on the ingestion rate and assimilation efficiency.
The relationship between the subcellular distribution of accumulated toxic metals into five operational fractions (subsequently combined into presumed detoxified and non-detoxified components) and ...toxicity in the clam Scrobicularia plana was investigated under different laboratory exposures. Clams were exposed to metal contaminated media (water and diet) and analysed for the partitioning of accumulated As, Cu and Zn into subcellular fractions. In general, metallothionein-like proteins, metal-rich granules and cellular debris in different proportions acted as main storage sites of accumulated metals in the clam soft tissues for these three metals. No significant differences were noted in the accumulation rates of As, Cu and Zn of groups of individuals with or without apparent signs of toxicity after up to 30 days of exposure to naturally contaminated sediment mixtures. There was, however, an increased proportional accumulation of Cu in the non-detoxified fraction with increased Cu accumulation rate in the clams, suggesting that the Cu uptake rate from contaminated sediments exceeded the combined rates of elimination and detoxification of Cu, with the subsequent likelihood for toxic effects in the clams.
The fouling barnacle Amphibalanus amphitrite is a cosmopolitan biomonitor of trace metal bioavailabilities, with an international comparative data set of body metal concentrations. Bioavailabilities ...of As, Cd, Cr, Cu, Fe, Mn, Pb, V and Zn to A. amphitrite were investigated at 19 sites along the Iranian coast of the understudied Persian Gulf. Commercial and fishing ports showed extremely high Cu bioavailabilities, associated with high Zn bioavailabilities, possibly from antifouling paints and procedures. V availability was raised at one port, perhaps associated with fuel leakage. Cd bioavailabilities were raised at sites near the Strait of Hormuz, perhaps affected by adjacent upwelling off Oman. The As data allow a reinterpretation of the typical range of accumulated As concentrations in A. amphitrite. The Persian Gulf data add a new region to the A. amphitrite database, confirming its importance in assessing the ecotoxicologically significant trace metal contamination of coastal waters across the world.
•Toxic metal pollution has been monitored in Persian Gulf coastal waters.•Metal bioavailabilities to a widespread fouling barnacle assessed by biomonitoring.•Variability between sites.•Examples of high copper, zinc, vanadium and cadmium bioavailabilities.•Valuable addition to a worldwide database to biomonitor coastal metal pollution.
Polychaete worms (Hediste diversicolor) originating from a strongly metal-contaminated area (Restronguet Creek) and a relatively clean site (Blackwater estuary) were exposed to a range of ...experimental doses of Ag, Cd, Cu and Zn. Specimens from both populations were compared to assess their relative sensitivity to metal stress and the physiological mechanisms involved in their respective adaptive strategies for coping with increased metal exposures. Taking into account the LC50 values, increased tolerance to Cd, Cu and Zn of the Restronguet Creek worms over that of the Blackwater was demonstrated, whereas the opposite was shown for Ag. An abundant secretion of mucus in response to toxicants was observed, possibly reducing metal availability for uptake, at least under laboratory conditions. This mechanism was particularly active in specimens from Restronguet Creek exposed to Ag and Cu. Unexpectedly, of the two worm populations, Blackwater worms contained significantly higher concentrations of cytosolic heat-stable compounds (CHSTC), a category of cytosolic components that includes metallothioneins, the detoxificatory role of which is well documented, and other compounds binding trace metals via sulphur bonds. However, the concentration of such compounds is not totally representative in itself of their involvement in metal detoxification, because a high rate of their turnover in metal-exposed worms might be responsible for (at least) the Cu storage associated with S in lysosomes as a consequence of the breakdown of Cu-thionein. Cu-containing lysosomes were abundant in epidermal cells of Restronguet Creek worms, but were lacking in Blackwater worms. Extracellular granules present in the epicuticle also contained S and Cu, their number and size being much more important in Restronguet Creek worms, and they appear to be a major detoxificatory store for accumulated Cu. Spherocrystals in cells of the gut wall seem to be the major detoxified store of Zn in Restronguet Creek worms, whereas in specimens from the Blackwater they were also present but contained only S and Ca at detectable levels. Evidence was also found for the presence of detoxificatory intracellular structures containing other metals and metalloids in the tegument and gut epithelium of Restronguet Creek worms. PUBLICATION ABSTRACT
