The extracellular vesicles of the helminth pathogen, Fasciola hepatica: biogenesis pathways and cargo molecules involved in parasite pathogenesis.

<p>Extracellular vesicles (EVs) released by parasites have important roles in establishing and maintaining infection. Analysis of the soluble and vesicular secretions of adult Fasciola hepatica has established a definitive characterisation of the total secretome of this zoonotic parasite. Fasciola secretes at least two sub-populations of EVs that differ according to size, cargo molecules and site of release from the parasite. The larger EVs are released from the specialised cells that line the parasite gastrodermus and contain the zymogen of the 37 kDa cathepsin L peptidase that performs a digestive function. The smaller exosome-like vesicle population originate from multivesicular bodies within the tegumental syncytium and carry many previously described immunomodulatory molecules that could be delivered into host cells. By integrating our proteomics data with recently available transcriptomic datasets we have detailed the pathways involved with EV biogenesis in F. hepatica and propose that the small exosome biogenesis occurs via ESCRT-dependent MVB formation in the tegumental syncytium before being shed from the apical plasma membrane. Furthermore, we found that the molecular machinery required for EV biogenesis is constitutively expressed across the intra-mammalian development stages of the parasite. By contrast, the cargo molecules packaged within the EVs are developmentally regulated, most likely to facilitate the parasites migration through host tissue and to counteract host immune attack.p>

Building Information Modelling (BIM) Software Interoperability: A Review of the Construction Sector

Building Information Modelling (BIM) is continuing to evolve and develop as the construction industry progresses towards level 2 maturity. However, one of the core barriers in this progression is the aspect of interoperability between software packages. This research and paper stems from a Knowledge Transfer Partnership (KTP) where both industry and academia come together to address this shortcoming within the sector. One of the core objectives of this partnership and the aim of this study is investigating potential solutions to this barrier, while also developing best working practices to be applied in industry. Using one of the case studies from this partnership (a temporary steel structure), this paper demonstrates a potential solution to addressing interoperability within structural analysis and detailing packages, MasterSeries and Revit respectively. The findings of the research indicate that a process based approach rather than that of additional software coding as being the preferred solution. The results of this preliminary research will aid in the development of the topic of interoperability within the sector, while also developing the knowledge and competencies of the parties within the KTP. The findings are explored further, by providing an overview of the resolution process adopted in this case study, in overcoming the interoperability that arose as the project progressed. It is envisaged that this study will assist the construction sector and its adoption of BIM technologies, while also addressing the critical aspect of operability between software.

Microbial transformations in phosphonate biosynthesis and catabolism, and their importance in nutrient cycling

Phosphorus cycling in the biosphere has traditionally been thought to involve almost exclusively transformations of the element in its pentavalent oxidation state. Recent evidence, however, suggests that a significant fraction of environmental phosphorus may exist in a more reduced form. Most abundant of these reduced phosphorus compounds are the phosphonates, with their direct carbon–phosphorus bonds, and striking progress has recently been made in elucidating the biochemistry of microbial phosphonate transformations. These advances are now presented in the context of their contribution to our understanding of phosphorus biogeochemistry and of such diverse fields as the productivity of the oceans, marine methanogenesis and the discovery of novel microbial antimetabolites.

The effect of polyphosphate kinase gene deletion on polyhydroxyalkanoate accumulation and carbon metabolism in Pseudomonas putida KT2440.

The primary enzyme involved in polyphosphate (polyP) synthesis, polyP kinase (ppk), has been deleted in Pseudomonas putida KT2440. This has resulted in a threefold to sixfold reduction in polyhydroxyalkanoate (PHA) accumulation compared with the wild type under conditions of nitrogen limitation, with either temperature or oxidative (H2O2) stress, when grown on glucose. The accumulation of PHA by Δppk mutant was the same as the wild type under nitrogen-limiting growth conditions. There was no difference in polyP levels between wild-type and Δppk strains under all growth conditions tested. In the Δppk mutant proteome, polyP kinase (PPK) was undetectable, but up-regulation of the polyp-associated proteins polyP adenosine triphosphate (ATP)/nicotinamide adenine dinucleotide (NAD) kinase (PpnK), a putative polyP adenosine monophosphate (AMP) phosphotransferase (PP_1752), and exopolyphosphatase was observed. Δppk strain exhibited significantly retarded growth with glycerol as carbon and energy source (42 h of lag period compared with 24 h in wild-type strain) but similar growth to the wild-type strain with glucose. Analysis of gene transcription revealed downregulation of glycerol kinase and the glycerol facilitator respectively. Glycerol kinase protein expression was also downregulated in the Δppk mutant. The deletion of ppk did not affect motility but reduced biofilm formation. Thus, the knockout of the ppk gene has resulted in a number of phenotypic changes to the mutant without affecting polyP accumulation.

Organophosphonates revealed: new insights into the microbial metabolism of ancient molecules.

Organophosphonates are ancient molecules that contain the chemically stable C–P bond, which is considered a relic of the reducing atmosphere on primitive earth. Synthetic phosphonates now have a wide range of applications in the agricultural, chemical and pharmaceutical industries. However, the existence of C–P compounds as contemporary biogenic molecules was not discovered until 1959, with the identification of 2-aminoethylphosphonic acid in rumen protozoa. Here, we review advances in our understanding of the biochemistry and genetics of microbial phosphonate metabolism, and discuss the role of these compounds and of the organisms engaged in their turnover within the P cycle.

M Dwarf Flare Continuum Variations on One-second Timescales: Calibrating and Modeling of ULTRACAM Flare Color Indices

We present a large data set of high-cadence dMe flare light curves obtained with custom continuum filters on the triple-beam, high-speed camera system ULTRACAM. The measurements provide constraints for models of the near-ultraviolet (NUV) and optical continuum spectral evolution on timescales of ≈1 s. We provide a robust interpretation of the flare emission in the ULTRACAM filters using simultaneously obtained low-resolution spectra during two moderate-sized flares in the dM4.5e star YZ CMi. By avoiding the spectral complexity within the broadband Johnson filters, the ULTRACAM filters are shown to characterize bona fide continuum emission in the NUV, blue, and red wavelength regimes. The NUV/blue flux ratio in flares is equivalent to a Balmer jump ratio, and the blue/red flux ratio provides an estimate for the color temperature of the optical continuum emission. We present a new “color-color” relationship for these continuum flux ratios at the peaks of the flares. Using the RADYN and RH codes, we interpret the ULTRACAM filter emission using the dominant emission processes from a radiative-hydrodynamic flare model with a high nonthermal electron beam flux, which explains a hot, T ≈ 104 K, color temperature at blue-to-red optical wavelengths and a small Balmer jump ratio as observed in moderate-sized and large flares alike. We also discuss the high time resolution, high signal-to-noise continuum color variations observed in YZ CMi during a giant flare, which increased the NUV flux from this star by over a factor of 100. Based on observations obtained with the Apache Point Observatory 3.5 m telescope, which is owned and operated by the Astrophysical Research Consortium, based on observations made with the William Herschel Telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofsica de Canarias, and observations, and based on observations made with the ESO Telescopes at the La Silla Paranal Observatory under programme ID 085.D-0501(A).

Metagenomic characterisation of the viral community of lough neagh, the largest freshwater lake in Ireland

<p>Lough Neagh is the largest and the most economically important lake in Ireland. It is also one of the most nutrient rich amongst the world's major lakes. In this study, 16S rRNA analysis of total metagenomic DNA from the water column of Lough Neagh has revealed a high proportion of Cyanobacteria and low levels of Actinobacteria, Acidobacteria, Chloroflexi, and Firmicutes. The planktonic virome of Lough Neagh has been sequenced and 2,298,791 2×300 bp Illumina reads analysed. Comparison with previously characterised lakes demonstrates that the Lough Neagh viral community has the highest level of sequence diversity. Only about 15% of reads had homologs in the RefSeq database and tailed bacteriophages (Caudovirales) were identified as a major grouping. Within the Caudovirales, the Podoviridae and Siphoviridae were the two most dominant families (34.3% and 32.8% of the reads with sequence homology to the RefSeq database), while ssDNA bacteriophages constituted less than 1% of the virome. Putative cyanophages were found to be abundant. 66,450 viral contigs were assembled with the largest one being 58,805 bp; its existence, and that of another 34,467 bp contig, in the water column was confirmed. Analysis of the contigs confirmed the high abundance of cyanophages in the water column.p>

Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia.

Candidaemia is the fourth most common cause of bloodstream infection, with a high mortality rate of up to 40%. Identification of host genetic factors that confer susceptibility to candidaemia may aid in designing adjunctive immunotherapeutic strategies. Here we hypothesize that variation in immune genes may predispose to candidaemia. We analyse 118,989 single-nucleotide polymorphisms (SNPs) across 186 loci known to be associated with immune-mediated diseases in the largest candidaemia cohort to date of 217 patients of European ancestry and a group of 11,920 controls. We validate the significant associations by comparison with a disease-matched control group. We observe significant association between candidaemia and SNPs in the CD58 (P = 1.97 × 10(-11); odds ratio (OR) = 4.68), LCE4A-C1orf68 (P = 1.98 × 10(-10); OR = 4.25) and TAGAP (P = 1.84 × 10(-8); OR = 2.96) loci. Individuals carrying two or more risk alleles have an increased risk for candidaemia of 19.4-fold compared with individuals carrying no risk allele. We identify three novel genetic risk factors for candidaemia, which we subsequently validate for their role in antifungal host defence.

Paleolimnology of selected Precambrian Shield lakes /

The analysis of fossil diatoms and Mallomonas assemblages in a 2.85 m sediment core revealed that a series of distinct floristic changes have occurred in the development of Found Lake, a small Shield lake in southern Ontario. Climatic and vegetational changes in the lake's watershed were closely associated with successional changes in the lake's biota. Nutrients released by the deciduous component of the Found Lake watershed appeared to be especially important in determining diatom and Mallomonas standing crop. The top 20 cm of sediment of 3 ,Shield lakes was then investigated using close interval (1 cm) analyses of diatoms, Mallomonas scales, pollen grains and sedimentary phosphorus. Found and Jake Lake are adjacent to Highway 60, whereas Delano Lake has been undisturbed and was used as a control. Dramatic changes in the diatom and Mallomonas communities were recorded in the Found and Jake Lake stratigraphies and could be closely associated with known historical events. Increased turbidity and nutrient enrichment were believed responsible for these successional changes. In addition, diatom and Mallomonas standing crop increased substantially following road construction in Found Lake's drainage basin. Meanwhile, no. sharp changes in diatom or Mallomonas communities were recorded in the recent sediments of the control (Delano) lake. The use£ulness o£ Synuracean scales as paleoindicators, as well as the importance o£ sectioning cores at close intervals during transition periods in a laker's development, was stressed.

Synthesis and Transformations of a Few Nitrogen and Oxygen Heterocycles

Department of Applied Chemistry, Cochin University of Science and Technology

Structural and biological investigations of metal complexes of some substituted thiosemicarbazones

Department of Applied Chemistry, Cochin University of Science and Technology