Chelating chloride using binuclear lanthanide complexes in water.

Halide recognition by supramolecular receptors and coordination complexes in water is a long-standing challenge. In this work, we report chloride binding in water and in competing media by pre-organised binuclear kinetically inert lanthanide complexes, bridged by flexible -(CH2)2- and -(CH2)3- spacers, forming [Ln2(DO3A)2C-2] and [Ln2(DO3A)2C-3], respectively. These hydrophilic, neutral lanthanide coordination complexes are shown to bind chloride with apparent association constants of up to 105 M-1 in water and in buffered systems. Hydroxide bridging was observed in these complexes at basic pH, which was proven to be overcome by chloride. Thus, these lanthanide complexes show promise towards chloride recognition in biology and beyond. The results described here have clearly identified a new area of anion coordination chemistry that is ripe for detailed exploration.

Translational research into intertemporal choice: the Western scrub-jay as an animal model for future-thinking.

Decisions often involve outcomes that will not materialise until later, and choices between immediate gratification and future consequences are thought to be important for human health and welfare. Combined human and animal research has identified impulsive intertemporal choice as an important factor in drug-taking and pathological gambling. In this paper, we give an overview of recent research into intertemporal choice in non-human animals, and argue that this work could offer insight into human behaviour through the development of animal models. As an example, we discuss the role of future-thinking in intertemporal choice, and review the case for the Western scrub-jay (Aphelocoma californica) as an animal model of such prospective cognition. This article is part of a Special Issue entitled: Tribute to Tom Zentall.

No evidence of temporal preferences in caching by Western scrub-jays (Aphelocoma californica).

Humans and other animals often favour immediate gratification over long-term gain. Primates, including humans, appear more willing to wait for rewards than other animals, such as rats or pigeons. Another group displaying impressive patience are the corvids, which possess large brains and show sophisticated cognitive abilities. Here, we assess intertemporal choice in one corvid species, the Western scrub-jay (Aphelocoma californica). These birds cache food for future consumption and respond flexibly to future needs. Cache-theft and cache-degradation are time-dependent processes in scrub-jay ecology that might necessitate sensitivity to delays between caching and retrieval. We adopt a caching paradigm with delays of up to 49 h. Across two experiments we find no evidence of a preference for earlier recovery. We highlight the possibility that, although scrub-jays can discriminate between the present and the future, they may not understand how far into the future an event will occur.

Thrombin generation using the calibrated automated thrombinoscope to assess reversibility of dabigatran and rivaroxaban.

The new direct-acting anticoagulants such as dabigatran and rivaroxaban are usually not monitored but may be associated with haemorrhage, particularly where renal impairment occurs. They have no effective "antidotes". We studied 17 patients receiving dabigatran 150 mg twice daily for non-valvular atrial fibrillation and 15 patients receiving rivaroxaban 10 mg daily for the prevention of deep venous thrombosis after hip or knee replacement surgery. We assessed the effect of these drugs on commonly used laboratory tests and Calibrated Automated Thrombogram (CAT) using plasma samples. We also assessed effects in fresh whole blood citrated patient samples using thromboelastography on the TEG and the ROTEM. The efficacy of nonspecific haemostatic agents prothrombin complex concentrate (PCC), Factor VIII Inhibitor By-passing Activity (FEIBA) and recombinant activated factor VII (rVIIa) were tested by reversal of abnormal thrombin generation using the CAT. Concentrations added ex vivo were chosen to reflect doses normally given in vivo. Dabigatran significantly increased the dynamic parameters of the TEG and ROTEM and the lag time of the CAT. It significantly reduced the endogenous thrombin potential (ETP) and reduced the peak height of the CAT. Rivaroxaban did not affect the TEG and ROTEM parameters but did increase the lag time and reduce ETP and peak height of the CAT. For both drugs, these parameters were significantly and meaningfully corrected by PCC and FEIBA and to a lesser but still significant extent by rFVIIa. These results may be useful in devising a reversal strategy in patients but clinical experience will be needed to verify them.

Re-caching by Western scrub-jays (Aphelocoma californica) cannot be attributed to stress.

Western scrub-jays (Aphelocoma californica) live double lives, storing food for the future while raiding the stores of other birds. One tactic scrub-jays employ to protect stores is "re-caching"-relocating caches out of sight of would-be thieves. Recent computational modelling work suggests that re-caching might be mediated not by complex cognition, but by a combination of memory failure and stress. The "Stress Model" asserts that re-caching is a manifestation of a general drive to cache, rather than a desire to protect existing stores. Here, we present evidence strongly contradicting the central assumption of these models: that stress drives caching, irrespective of social context. In Experiment (i), we replicate the finding that scrub-jays preferentially relocate food they were watched hiding. In Experiment (ii) we find no evidence that stress increases caching. In light of our results, we argue that the Stress Model cannot account for scrub-jay re-caching.

Luminescence and upconversion from thulium(III) species in solution.

Thulium salts and complexes are shown to be emissive from three states in the excited state manifold of Tm(3+). Formation of the (1)D(2) state can result in luminescence, or in energy transfer to the lower energy (1)G(4) and (3)H(4) emissive states. Where chromophores are present in the ligand structure, emission is restricted to thulium centred emissive states that are lower in energy than the chromophore centred donor state. We have also observed direct multi-photon excitation of the thulium excited state manifold. Furthermore, additional transitions are observed in the multi-photon excitation spectra that are consistent with upconversion as a consequence of sequential single photon absorption and relaxation processes within the thulium excited state manifold.

A novel ABCA1 nonsense mutation, R1270X, in Tangier disease associated with an unrecognised bleeding tendency.

The ATP binding cassette transporter A1 (ABCA1) is involved in the regulation of lipid trafficking and export of cholesterol from cells to high density lipoprotein (HDL). ABCA1 gene defects cause Tangier disease, an autosomal recessive disorder characterised by the absence of HDL-cholesterol in plasma, abnormal deposition of cholesteryl esters in the reticuloendothelial system, defective platelet dense and lysosomal granule release, and disordered cellular cholesterol efflux. We describe the case of a 62-year-old man with Tangier disease who presented with severe anaemia secondary to a spontaneous splenic haematoma. He underwent elective splenectomy without haemorrhage and his thrombocytopaenia resolved with a platelet count rising from 97 to 560 x 10(9)/L. Macroscopically, the resected spleen was enlarged with evidence of splenic haematoma. Histologic analysis of sections of spleen revealed lipid histiocytosis consistent with the diagnosis of Tangier disease. DNA sequence analysis revealed the subject to be a homozygote for a novel ABCA1 mutation c.4121C>T, which changes arginine 1270 to a stop codon (R1270X). In conclusion, we describe a case of Tangier disease in association with an unrecognised bleeding tendency, in a man homozygous for a novel ABCA1 gene mutation, R1270X.

Phase 1/2 study of fractionated (131)I-rituximab in low-grade B-cell lymphoma: the effect of prior rituximab dosing and tumor burden on subsequent radioimmunotherapy.

The effect of induction therapy with multiple doses of rituximab on the subsequent efficacy and toxicity of anti-CD20 radioimmunotherapy is unknown. We evaluated a novel protocol using 4 weekly infusions of 375 mg/m(2) rituximab followed by 2 fractions of (131)I-rituximab, preceded by a 100-mg/m(2) predose of rituximab, in relapsed indolent B-cell lymphoma. Induction therapy with rituximab significantly increased the effective half-life of (131)I-rituximab (P = .003) and high serum levels of rituximab after induction therapy correlated with increased effective half-life of the radioimmunoconjugate (P = .009). Patients with large tumor burdens experienced significant increases in the effective half-life of (131)I-rituximab between delivery of the first and second fractions (P = .007). Induction therapy with multiple doses of rituximab did not appear to compromise the clinical efficacy or increase toxicity of subsequent (131)I-rituximab radioimmunotherapy. The overall response rate was 94%, with complete response rate 50%. The median time to progression was 20 months, significantly longer than for the last qualifying chemotherapy (P = .001). Fractionation of (131)I-rituximab allowed cumulative whole-body doses of more than 120 cGy, approximately 60% greater than those previously achieved with a single administration of a murine radioimmunconjugate, to be delivered without significant hematologic toxicity.

Biologically induced mineralization of dypingite by cyanobacteria from an alkaline wetland near Atlin, British Columbia, Canada.

BACKGROUND: This study provides experimental evidence for biologically induced precipitation of magnesium carbonates, specifically dypingite (Mg5(CO3)4(OH)2.5H2O), by cyanobacteria from an alkaline wetland near Atlin, British Columbia. This wetland is part of a larger hydromagnesite (Mg5(CO3)4(OH)2.4H2O) playa. Abiotic and biotic processes for magnesium carbonate precipitation in this environment are compared. RESULTS: Field observations show that evaporation of wetland water produces carbonate films of nesquehonite (MgCO3.3H2O) on the water surface and crusts on exposed surfaces. In contrast, benthic microbial mats possessing filamentous cyanobacteria (Lyngbya sp.) contain platy dypingite (Mg5(CO3)4(OH)2.5H2O) and aragonite. Bulk carbonates in the benthic mats (delta13C avg. = 6.7%, delta 18O avg. = 17.2%) were isotopically distinguishable from abiotically formed nesquehonite (delta13C avg. = 9.3%, delta 18O avg. = 24.9%). Field and laboratory experiments, which emulated natural conditions, were conducted to provide insight into the processes for magnesium carbonate precipitation in this environment. Field microcosm experiments included an abiotic control and two microbial systems, one containing ambient wetland water and one amended with nutrients to simulate eutrophic conditions. The abiotic control developed an extensive crust of nesquehonite on its bottom surface during which [Mg2+] decreased by 16.7% relative to the starting concentration. In the microbial systems, precipitation occurred within the mats and was not simply due to the capturing of mineral grains settling out of the water column. Magnesium concentrations decreased by 22.2% and 38.7% in the microbial systems, respectively. Laboratory experiments using natural waters from the Atlin site produced rosettes and flakey globular aggregates of dypingite precipitated in association with filamentous cyanobacteria dominated biofilms cultured from the site, whereas the abiotic control again precipitated nesquehonite. CONCLUSION: Microbial mats in the Atlin wetland create ideal conditions for biologically induced precipitation of dypingite and have presumably played a significant role in the development of this natural Mg-carbonate playa. This biogeochemical process represents an important link between the biosphere and the inorganic carbon pool.