Helminth infection-induced malignancy

Infectious diseases cause more than 20% of cancers in the developing world [1]. About a dozen pathogens including Epstein-Barr virus and human T cell lymphocytotropic virus 1 are among the well-known examples. In addition, infection with several trematodes, which are eukaryotes, can cause malignancy. The International Agency for Research on Cancer categorizes infection with the fish-borne trematodes Opisthorchis viverrini and Clonorchis sinensis and the blood fluke Schistosoma haematobium as Group 1 biological carcinogens [2]. In addition to parasitism directly damaging development, health, and prosperity of infected populations, infection with these helminths leads to cholangiocarcinoma (CCA) (bile duct cancer) and squamous cell carcinoma (SCC) of the urinary bladder, respectively [2]. By contrast, infection with phylogenetic relatives, also trematodes of the phylum Platyhelminthes and also major pathogens, is not carcinogenic. These irregularities suggest that either helminth-specific metabolites contribute to tumorigenesis and/or that certain tissues or organs are particularly susceptible to infection-induced malignancy. Moreover, each of these helminth infections must be viewed holistically in the context of a perfect storm of risk for cancer (see [3])

Helminth Infection-Induced Malignancy.

Infectious diseases cause more than 20% of cancers in the developing world [1]. About a dozen pathogens including Epstein-Barr virus and human T cell lymphocytotropic virus 1 are among the well-known examples. In addition, infection with several trematodes, which are eukaryotes, can cause malignancy. The International Agency for Research on Cancer categorizes infection with the fish-borne trematodes Opisthorchis viverrini and Clonorchis sinensis and the blood fluke Schistosoma haematobium as Group 1 biological carcinogens [2]. In addition to parasitism directly damaging development, health, and prosperity of infected populations, infection with these helminths leads to cholangiocarcinoma (CCA) (bile duct cancer) and squamous cell carcinoma (SCC) of the urinary bladder, respectively [2]. By contrast, infection with phylogenetic relatives, also trematodes of the phylum Platyhelminthes and also major pathogens, is not carcinogenic. These irregularities suggest that either helminth-specific metabolites contribute to tumorigenesis and/or that certain tissues or organs are particularly susceptible to infection-induced malignancy. Moreover, each of these helminth infections must be viewed holistically in the context of a perfect storm of risk for cancer (see [3])

Genetic manipulation of schistosomes - Progress with integration competent vectors

Draft genome sequences for Schistosoma japonicum and S. mansoni are now available. The schistosome genome encodes ∼13 000 protein-encoding genes for which the functions of few are well understood. Nonetheless, the new genes represent potential intervention targets, and molecular tools are being developed to determine their importance. Over the past 15 years, noteworthy progress has been achieved towards development of tools for gene manipulation and transgenesis of schistosomes. A brief history of genetic manipulation is presented, along with a review of the field with emphasis on reports of integration of transgenes into schistosome chromosomes

Recurrent cerebellar architecture solves the motor-error problem

Current views of cerebellar function have been heavily influenced by the models of Marr and Albus, who suggested that the climbing fibre input to the cerebellum acts as a teaching signal for motor learning. It is commonly assumed that this teaching signal must be motor error (the difference between actual and correct motor command), but this approach requires complex neural structures to estimate unobservable motor error from its observed sensory consequences. We have proposed elsewhere a recurrent decorrelation control architecture in which Marr-Albus models learn without requiring motor error. Here, we prove convergence for this architecture and demonstrate important advantages for the modular control of systems with multiple degrees of freedom. These results are illustrated by modelling adaptive plant compensation for the three-dimensional vestibular ocular reflex. This provides a functional role for recurrent cerebellar connectivity, which may be a generic anatomical feature of projections between regions of cerebral and cerebellar cortex

Contrasting Observed Atmospheric Responses to Tropical Sea Surface Temperature Warming Patterns

AM was funded by a NERC doctoral training partnership grant (NE/L002558/1). This study was funded as part of NERC's support of the National Center for Earth Observation: HB and PIP were supported by grant number NE/R016518/1.Equilibrium climate sensitivity (ECS) is a theoretical concept which describes the change in global mean surface temperature that results from a sustained doubling of atmospheric CO2. Current ECS estimates range from ∼1.8 to 5.6 K, reflecting uncertainties in climate feedbacks. The sensitivity of the lower (1,000–700 hPa) and upper (500–200 hPa) troposphere to changes in spatial patterns of tropical sea surface temperature (SST) have been proposed by recent model studies as key feedbacks controlling climate sensitivity. We examine empirical evidence for these proposed mechanisms using 14 years of satellite data. We examine the response of temperature and humidity profiles, clouds, and top‐of‐the‐atmosphere radiation to relative warming in tropical ocean regions when there is either strong convection or subsidence. We find warmer SSTs in regions of strong subsidence are coincident with a decrease in lower tropospheric stability (−0.9 ± 0.4 KK−1) and low cloud cover (∼−6% K−1). This leads to a warming associated with the weakening in the shortwave cooling effect of clouds (4.2 ± 1.9 Wm−2K−1), broadly consistent with model calculations. In contrast, warmer SSTs in regions of strong convection are coincident with an increase in upper tropospheric humidity (3.2 ± 1.5% K−1). In this scenario, the dominant effect is the enhancement of the warming longwave cloud radiative effect (3.8 ± 3.0 Wm−2K−1) from an increase in high cloud cover (∼7% K−1), though changes in the net (longwave and shortwave) effect are not statistically significant (p < 0.003). Our observational evidence supports the existence of mechanisms linking contrasting atmospheric responses to patterns in SST, mechanisms which have been linked to climate sensitivity.Publisher PDFPeer reviewe

Generating vague geographic information through data mining of passive web data

Vagueness is an inherent property of geographic data. This thesis develops a geocomputational method that demonstrates that vague information has the potential to be incorporated within GIS in straightforward manner. This method applies vagueness to the elements of place: types, names and spatial boundaries, generating vague geographic objects by extracting and filtering the differing opinions and perceptions held within web derived data. The aim of the research is threefold: (1) to investigate an approach to automatically generate vague, probabilistic geographical information concerning place by mining differing perspectives from passive web data; (2) to assure the quality of the vague information produced and test the hypothesis that its results are indistinguishable from directly surveying public opinion; and (3) to demonstrate the value of integrating vague information into geospatial applications via examples of its use. To achieve the first aim, the thesis develops methods to extract differing perspectives of place from web data - constructing (i) vague place type settlement classification and (ii) vague place names and boundaries for ‘neighbourhood’ level units. The methods developed are automated, suitable for generating output at a national scale and use a wide range of different source data to collect the differing opinions. The second aim assesses the quality of the data produced, determining if output extracted from the web was representative of that obtained from asking people directly. Statistical analysis of regression models demonstrates that data were representative of that collected through asking people directly both for vague settlement classifications and vague urban locale boundaries. Importantly, the validation data, drawn from public opinion, also supported the notion that vagueness was omnipresent within geographic information concerning place. The third aim was addressed through the use of case studies in order to demonstrate the added value of such data and subsequent integration of vague geographic objects within other socio-economic data. Critically, the incorporation of vagueness within place models not only add value to geographic data but also improve the accuracy of real-world representations within GIS

Characterization of SR3 reveals abundance of non-LTR retrotransposons of the RTE clade in the genome of the human blood fluke, Schistosoma mansoni

BACKGROUND: It is becoming apparent that perhaps as much as half of the genome of the human blood fluke Schistosoma mansoni is constituted of mobile genetic element-related sequences. Non-long terminal repeat (LTR) retrotransposons, related to the LINE elements of mammals, comprise much of this repetitive component of the schistosome genome. Of more than 12 recognized clades of non-LTR retrotransposons, only members of the CR1, RTE, and R2 clades have been reported from the schistosome genome. RESULTS: Inspection of the nucleotide sequence of bacterial artificial chromosome number 49_J_14 from chromosome 1 of the genome of Schistosoma mansoni (GenBank AC093105) revealed the likely presence of several RTE-like retrotransposons. Among these, a new non-LTR retrotransposon designated SR3 was identified and is characterized here. Analysis of gene structure and phylogenetic analysis of both the reverse transcriptase and endonuclease domains of the mobile element indicated that SR3 represented a new family of RTE-like non-LTR retrotransposons. Remarkably, two full-length copies of SR3-like elements were present in BAC 49-J-14, and one of 3,211 bp in length appeared to be intact, indicating SR3 to be an active non-LTR retrotransposon. Both were flanked by target site duplications of 10–12 bp. Southern hybridization and bioinformatics analyses indicated the presence of numerous copies (probably >1,000) of SR3 interspersed throughout the genome of S. mansoni. Bioinformatics analyses also revealed SR3 to be transcribed in both larval and adult developmental stages of S. mansoni and to be also present in the genomes of the other major schistosome parasites of humans, Schistosoma haematobium and S. japonicum. CONCLUSION: Numerous copies of SR3, a novel non-LTR retrotransposon of the RTE clade are present in the genome of S. mansoni. Non-LTR retrotransposons of the RTE clade including SR3 appear to have been remarkably successful in colonizing, and proliferation within the schistosome genome

Observed and CMIP5‐Simulated Radiative Flux Variability Over West Africa

We explore the ability of general circulation models in the Coupled Model Intercomparison Project (CMIP5) to recreate observed seasonal variability in top‐of‐the‐atmosphere and surface radiation fluxes over West Africa. This tests CMIP5 models' ability to describe the radiative energy partitioning, which is fundamental to our understanding of the current climate and its future changes. We use 15 years of the monthly Clouds and the Earth's Radiant Energy System Energy Balanced and Filled (EBAF) product, alongside other satellite, reanalysis, and surface station products. We find that the CMIP5 multimodel mean is generally within the reference product range, with annual mean CMIP5 multimodel mean—EBAF of −0.5 W m−2 for top‐of‐the‐atmosphere reflected shortwave radiation, and 4.6 W m−2 in outgoing longwave radiation over West Africa. However, the range in annual mean of the model seasonal cycles is large (37.2 and 34.0 W m−2 for reflected shortwave radiation and outgoing longwave radiation, respectively). We use seasonal and regional contrasts in all‐sky fluxes to infer that the representation of the West African monsoon in numerical models affects radiative energy partitioning. Using clear‐sky surface fluxes, we find that the models tend to have more downwelling shortwave and less downwelling longwave radiation than EBAF, consistent with past research. We find models that are drier and have lower aerosol loading tend to show the largest differences. We find evidence that aerosol variability has a larger effect in modulating downwelling shortwave radiation than water vapor in EBAF, while the opposite effect is seen in the majority of CMIP5 models.ISSN:2333-508

A bug’s life: Delving into the challenges of helminth microbiome studies

The body of vertebrates is inhabited by trillions of microorganisms, i.e. viruses, archaea, bacteria and unicellular eukaryotes, together referred to as the ‘microbiota’. Similarly, vertebrates also host a plethora of parasitic worms (the ‘macrobiota’), some of which share their environment with the microbiota inhabiting the gastrointestinal tract [1]. Complex interactions between the helminths and the gut microbiota have been associated with establishment of parasite infection, disease manifestations, and host immune-modulation [2, 3]. Remarkably, not only enteric helminths alter the 26 gut microbiome composition [4], but also the infection with blood flukes of the genus Schistosoma has been associated to intestinal dysbiosis even before the onset of egg laying [5, 6]. Comparably, over the last decade, evidence has emerged of the contribution(s) of the resident microbiota to several physiological and reproductive processes of invertebrate hosts, including insects, arachnids, worms and snails [7, 8]. These noteworthy discoveries, coupled with 30 the recent expansion of high-throughput microbiota- and microbiome-profiling approaches (the former referring to a community of microorganisms themselves, and the latter to the microorganisms and their genomes, in a ecological niche), are rapidly leading to a much better understanding of the composition and functions of microbial communities inhabiting parasitic worms of major public health and socio-economic significance. This basic knowledge might expose exploitable vulnerabilities of parasites, paving the way to the development of novel control strategies [9]