The population dynamics of the crested newt (Triturus Cristatus Cristatus (Laurenti)).

This thesis describes studies carried out on the crested newt, Triturus cristatus, and the smooth newt, T. vulgaris, at two localities in the vicinity of Milton Keynes, Buckinghamshire, between 1980 and 1983. The first study site was a pond within the grounds of the Open University at Walton Hall and the second was some 8 miles away from this near the village of Milton Bryan. At Walton Hall crested newts were intercepted during migration to the breeding pond using drift fencing and pitfall traps and by picking animals up off the road during evening searches. In this way it was found that movement was significantly correlated with daily temperature, but not with daily rainfall. In addition, it was observed that males entered the breeding pond significantly earlier than the females. At Milton Bryan a program of mark-recapture analyses was carried out on both species as the basis for the study of their population dynamics. Animals were trapped using static underwater traps and marked using toe-clips and the recording of belly-patterning. Both species were found to show variable population sizes from year to year. The sex ratio in T. vulgaris showed an excess of females in all years, whilst that of T. cristatus varied from an excess of males in some years to equality in other years. Annual survival of male and female crested newts was calculated as 0.36 for each sex. From data on weight change during the season it was found that the majority of individuals of both sexes lost weight whilst in the water. Annual growth in the crested newt was found to be highly variable, but positively correlated with body size; smaller individuals had larger increments of growth than larger individuals. However, animals of the same size did not necessarily grow by the same amount. Size-frequency distributions of both species are analysed and morphometric characteristics compared with data from other populations. The problems associated with the the extrapolation of these types of data into age-distributions are discussed, with reference to the data on growth. It is concluded that length cannot be used as reliable indicator of age in T. cristatus. From the size-frequency data it was found that the numbers of juveniles appearing at a breeding site may be highly variable from year to year. The implications of this for the dynamics of crested newt populations are discussed. Data are also presented from the dissection of preserved animals. These relate gonad size to body size in both species. It is shown that both testes weight and ovary weight are positively correlated with body weight and snout-vent length and that females display size-specific fecundity i.e. larger females produce larger ova and greater quantities of ova than smaller individuals. These findings are discussed with reference to other species of urodele and with regard to the life history tactics displayed by other species

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin

Biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom

Oceanic harmful algal blooms of Pseudo-nitzschia diatoms produce the potent mammalian neurotoxin domoic acid (DA). Despite decades of research, the molecular basis for its biosynthesis is not known. By using growth conditions known to induce DA production in Pseudo-nitzschia multiseries, we implemented transcriptome sequencing in order to identify DA biosynthesis genes that colocalize in a genomic four-gene cluster. We biochemically investigated the recombinant DA biosynthetic enzymes and linked their mechanisms to the construction of DA's diagnostic pyrrolidine skeleton, establishing a model for DA biosynthesis. Knowledge of the genetic basis for toxin production provides an orthogonal approach to bloom monitoring and enables study of environmental factors that drive oceanic DA production

Atomic Layer Deposition of the Solid Electrolyte Garnet Li₇La₃Zr₂O₁₂

Lithium solid electrolytes are a promising platform for achieving high energy density, long-lasting, and safe rechargeable batteries, which could have widespread societal impact. In particular, the ceramic oxide garnet Li₇La₃Zr₂O₁₂ (LLZO) has been shown to be a promising electrolyte due to its stability and high ionic conductivity. Two major challenges for commercialization are the manufacture of thin layers and the creation of stable, low-impedance interfaces with both anode and cathode materials. Atomic layer deposition (ALD) has recently been shown to be a powerful method for depositing both solid electrolytes and interfacial layers to improve the stability and performance at electrode–electrolyte interfaces in battery systems. Herein, we present a thermal ALD process for LLZO, demonstrating the ability to tune composition within the amorphous as-deposited film, which is studied using in situ quartz crystal microbalance measurements. Postannealing using a variety of substrates and gas environments was performed, and the formation of the cubic phase was observed at temperatures as low as 555 °C, significantly lower than what is required for bulk processing. Additionally, challenges associated with achieving a dense garnet phase due to substrate reactivity, morphology changes, and Li loss under the necessary high-temperature annealing are quantified via in situ synchrotron X-ray diffraction

Mendelian randomization evaluation of causal effects of fibrinogen on incident coronary heart disease.

BackgroundFibrinogen is an essential hemostatic factor and cardiovascular disease risk factor. Early attempts at evaluating the causal effect of fibrinogen on coronary heart disease (CHD) and myocardial infraction (MI) using Mendelian randomization (MR) used single variant approaches, and did not take advantage of recent genome-wide association studies (GWAS) or multi-variant, pleiotropy robust MR methodologies.Methods and findingsWe evaluated evidence for a causal effect of fibrinogen on both CHD and MI using MR. We used both an allele score approach and pleiotropy robust MR models. The allele score was composed of 38 fibrinogen-associated variants from recent GWAS. Initial analyses using the allele score used a meta-analysis of 11 European-ancestry prospective cohorts, free of CHD and MI at baseline, to examine incidence CHD and MI. We also applied 2 sample MR methods with data from a prevalent CHD and MI GWAS. Results are given in terms of the hazard ratio (HR) or odds ratio (OR), depending on the study design, and associated 95% confidence interval (CI). In single variant analyses no causal effect of fibrinogen on CHD or MI was observed. In multi-variant analyses using incidence CHD cases and the allele score approach, the estimated causal effect (HR) of a 1 g/L higher fibrinogen concentration was 1.62 (CI = 1.12, 2.36) when using incident cases and the allele score approach. In 2 sample MR analyses that accounted for pleiotropy, the causal estimate (OR) was reduced to 1.18 (CI = 0.98, 1.42) and 1.09 (CI = 0.89, 1.33) in the 2 most precise (smallest CI) models, out of 4 models evaluated. In the 2 sample MR analyses for MI, there was only very weak evidence of a causal effect in only 1 out of 4 models.ConclusionsA small causal effect of fibrinogen on CHD is observed using multi-variant MR approaches which account for pleiotropy, but not single variant MR approaches. Taken together, results indicate that even with large sample sizes and multi-variant approaches MR analyses still cannot exclude the null when estimating the causal effect of fibrinogen on CHD, but that any potential causal effect is likely to be much smaller than observed in epidemiological studies

The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis

Background: A high circulating concentration of interleukin 6 is associated with increased risk of coronary heart disease. Blockade of the interleukin-6 receptor (IL6R) with a monoclonal antibody (tocilizumab) licensed for treatment of rheumatoid arthritis reduces systemic and articular inflammation. However, whether IL6R blockade also reduces risk of coronary heart disease is unknown. Methods: Applying the mendelian randomisation principle, we used single nucleotide polymorphisms (SNPs) in the gene IL6R to evaluate the likely efficacy and safety of IL6R inhibition for primary prevention of coronary heart disease. We compared genetic findings with the effects of tocilizumab reported in randomised trials in patients with rheumatoid arthritis. Findings: In 40 studies including up to 133 449 individuals, an IL6R SNP (rs7529229) marking a non-synonymous IL6R variant (rs8192284; p.Asp358Ala) was associated with increased circulating log interleukin-6 concentration (increase per allele 9.45%, 95% CI 8.34-10.57) as well as reduced C-reactive protein (decrease per allele 8.35%, 95% CI 7.31-9.38) and fibrinogen concentrations (decrease per allele 0.85%, 95% CI 0.60-1.10). This pattern of effects was consistent with IL6R blockade from infusions of tocilizumab (4-8 mg/kg every 4 weeks) in patients with rheumatoid arthritis studied in randomised trials. In 25 458 coronary heart disease cases and 100 740 controls, the IL6R rs7529229 SNP was associated with a decreased odds of coronary heart disease events (per allele odds ratio 0.95, 95% CI 0.93-0.97, p=1.53x10(-5)). Interpretation: On the basis of genetic evidence in human beings, IL6R signalling seems to have a causal role in development of coronary heart disease. IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomised trials. Genetic studies in populations could be used more widely to help to validate and prioritise novel drug targets or to repurpose existing agents and targets for new therapeutic uses