Five year prognosis in patients with angina identified in primary care : incident cohort study

Peer reviewedPublisher PD

Identifying overlooked mechanisms for organic phosphorus and nitrogen acquisition in environmental bacteria

All living organisms require phosphorus (P) and nitrogen (N), which exist in many forms, from inorganic phosphate (Pi) or ammonium, to multiple and diverse organic P (Po) and N molecules. As essential elements, bacteria possess multiple mechanisms that allow them to acquire P and N from their surrounding environment. Many environmental niches, including regions of the global ocean and the rhizosphere of crop plants, exhibit N and P limitation, and thus bacteria must possess mechanisms to overcome this nutrient limitation. Over the past seven years, I have contributed to, and led, research uncovering hitherto overlooked mechanisms for N and P acquisition and characterising others. This research has resulted in several published papers, including two first author papers within this field as outputs. In particular, I have contributed to research into the mechanisms displayed by rhizobacteria associated with oilseed rape (Brassica napus), including Pseudomonas and Flavobacteria spp., using analysis of proteomics data. The biological insights provided from this work were used to develop further foci of study, including the activity, functional role and distribution of a newly identified phosphatase, and the extracellular activity of Po-mineralising enzymes and its consequences for Pi availability. I have also led research into the identification, characterisation, and environmental distribution of 2-aminoethylphosphonate (2AEP) transporters, showing a novel 2AEP transporter to be the most transcribed phosphonate transporter in the global ocean. I followed this research with further investigation into the molecular mechanisms underpinning the regulation of 2AEP transport and degradation in Pseudomonas putida BIRD-1. By utilising my developed skill sets in both wet lab and bioinformatics techniques, I also contributed to papers investigating lipid remodelling, a mechanism by which bacteria reduce the quantity of phospholipids in their lipid membranes, in both environmental and pathogenic bacteria. Additionally, I have contributed to, and written, other papers within the field of environmental microbiology, which go beyond the scope of this thesis. As such, the works presented in this thesis represent a coherent body of work demonstrating my contribution to the research field

Relationships of Biomass-Burning Aerosols to Ice in Orographic Wave Clouds

Ice concentrations in orographic wave clouds at temperatures between −24° and −29°C were shown to be related to aerosol characteristics in nearby clear air during five research flights over the Rocky Mountains. When clouds with influence from colder temperatures were excluded from the dataset, mean ice nuclei and cloud ice number concentrations were very low, on the order of 1–5 L^(−1). In this environment, ice number concentrations were found to be significantly correlated with the number concentration of larger particles, those larger than both 0.1- and 0.5-μm diameter. A variety of complementary techniques was used to measure aerosol size distributions and chemical composition. Strong correlations were also observed between ice concentrations and the number concentrations of soot and biomass-burning aerosols. Ice nuclei concentrations directly measured in biomass-burning plumes were the highest detected during the project. Taken together, this evidence indicates a potential role for biomass-burning aerosols in ice formation, particularly in regions with relatively low concentrations of other ice nucleating aerosols

Observation of playa salts as nuclei in orographic wave clouds

During the Ice in Clouds Experiment-Layer Clouds (ICE-L), dry lakebed, or playa, salts from the Great Basin region of the United States were observed as cloud nuclei in orographic wave clouds over Wyoming. Using a counterflow virtual impactor in series with a single-particle mass spectrometer, sodium-potassium-magnesium-calcium-chloride salts were identified as residues of cloud droplets. Importantly, these salts produced similar mass spectral signatures to playa salts with elevated cloud condensation nuclei (CCN) efficiencies close to sea salt. Using a suite of chemical characterization instrumentation, the playa salts were observed to be internally mixed with oxidized organics, presumably produced by cloud processing, as well as carbonate. These salt particles were enriched as residues of large droplets (>19 μm) compared to smaller droplets (>7 μm). In addition, a small fraction of silicate-containing playa salts were hypothesized to be important in the observed heterogeneous ice nucleation processes. While the high CCN activity of sea salt has been demonstrated to play an important role in cloud formation in marine environments, this study provides direct evidence of the importance of playa salts in cloud formation in continental North America has not been shown previously. Studies are needed to model and quantify the impact of playas on climate globally, particularly because of the abundance of playas and expected increases in the frequency and intensity of dust storms in the future due to climate and land use changes

Clinical effectiveness and cost-effectiveness of open and arthroscopic rotator cuff repair [the UK Rotator Cuff Surgery (UKUFF) randomised trial]

Peer reviewedPublisher PD

A distinct, high-affinity, alkaline phosphatase facilitates occupation of P-depleted environments by marine picocyanobacteria

Marine picocyanobacteria of the genera Prochlorococcus and Synechococcus, the two most abundant phototrophs on Earth, thrive in oligotrophic oceanic regions. While it is well known that specific lineages are exquisitely adapted to prevailing in situ light and temperature regimes, much less is known of the molecular machinery required to facilitate occupancy of these low-nutrient environments. Here, we describe a hitherto unknown alkaline phosphatase, Psip1, that has a substantially higher affinity for phosphomonoesters than other well-known phosphatases like PhoA, PhoX, or PhoD and is restricted to clade III Synechococcus and a subset of high light I-adapted Prochlorococcus strains, suggesting niche specificity. We demonstrate that Psip1 has undergone convergent evolution with PhoX, requiring both iron and calcium for activity and likely possessing identical key residues around the active site, despite generally very low sequence homology. Interrogation of metagenomes and transcriptomes from TARA oceans and an Atlantic Meridional transect shows that psip1 is abundant and highly expressed in picocyanobacterial populations from the Mediterranean Sea and north Atlantic gyre, regions well recognized to be phosphorus (P)-deplete. Together, this identifies psip1 as an important oligotrophy-specific gene for P recycling in these organisms. Furthermore, psip1 is not restricted to picocyanobacteria and is abundant and highly transcribed in some α-proteobacteria and eukaryotic algae, suggesting that such a high-affinity phosphatase is important across the microbial taxonomic world to occupy low-P environments.</p

Five-Year Prognosis in an Incident Cohort of People Presenting with Acute Myocardial Infarction

Peer reviewedPublisher PD