Multiple problems in siblings with Gardner’s syndrome

The problems encountered in the diagnosis of two siblings suffering from a high penetration variant of Gardner’s syndrome are presented. The importance of recognizing the extra colonic manifestations of the syndrome at an early stage and technical difficulties encountered during colonoscopy are noted. Operative procedures available to treat multiple colonic polyps in Gardner’s syndrome are discussed in relation to technical problems which may be encountered in the individual case. Hopefully this presentation will highlight the importance of the setting up of a Familial Polyposis Coli register in Malta in order to facilitate early diagnoses and treatment of the condition.peer-reviewe

Hepatitis B immunisation : a survey of surgeons and theatre nurses

Acute viral hepatitis remains a serious condition. Its long-term sequelae include cirrhosis and hepatocellular carcinoma. Health workers constitute a high-risk group for contracting hepatitis B. A group of clinicians associated with invasive procedures and nurses working in operating theatres were invited to answer a confidential questionnaire concerning hepatitis B immunisation and the use of protective measures. A self-administered confidential questionnaire was sent to 152 clinicians and 97 theatre nurses, of whom 82 and 74 respectively responded, giving an overall response rate of 63 %. Whilst 91% of respondents considered their speciality as being of high risk for hepatitis B only 63% of them were fully immunised and of these only 51% had had their immunity tested. Out of those who checked their antibody status 19% did so following a needle stick injury. 60% of our respondents had had a needle stick injury over the past year. Even so barrier precaution techniques were used infrequently with only 17% always or at least frequently using double gloving and 10% wearing a visor during operations. Some respondents also commented on the poor availability of resources such as impermeable gowns or blunt needles which are established precautions against contamination from hepatitis B.peer-reviewe

Khat-Chewing, Adiaphorisation and Morality: Rethinking Ethics in the Age of the Synopticon

In June 2014, the UK Government made khat (Catha edulis) a Class C drug under the UK Misuse of Drugs Act. Based on limited evidence, this decision went against the Government's own Advisory Council on the Misuse of Drugs and has divided members of the British–Somali diaspora, where khat is a popular form of recreation. The Government’s decision to ban khat highlights broader questions regarding how ethical legislation is implemented within post-industrial societies, exposing postcolonial power systems that ‘Other’ migrant groups through synoptic control. Based on qualitative interviews with members of the Somali diaspora and external agencies in Northern England, the research explores how this system fails to consider khat's complex moral position while framing users and those living within the diaspora as deviant

DISMISS: detection of stranded methylation in MeDIP-Seq data

BACKGROUND: DNA methylation is an important regulator of gene expression and chromatin structure. Methylated DNA immunoprecipitation sequencing (MeDIP-Seq) is commonly used to identify regions of DNA methylation in eukaryotic genomes. Within MeDIP-Seq libraries, methylated cytosines can be found in both double-stranded (symmetric) and single-stranded (asymmetric) genomic contexts. While symmetric CG methylation has been relatively well-studied, asymmetric methylation in any dinucleotide context has received less attention. Importantly, no currently available software for processing MeDIP-Seq reads is able to resolve these strand-specific DNA methylation signals. Here we introduce DISMISS, a new software package that detects strand-associated DNA methylation from existing MeDIP-Seq analyses. RESULTS: Using MeDIP-Seq datasets derived from Apis mellifera (honeybee), an invertebrate species that contains more asymmetric- than symmetric- DNA methylation, we demonstrate that DISMISS can identify strand-specific DNA methylation signals with similar accuracy as bisulfite sequencing (BS-Seq; single nucleotide resolution methodology). Specifically, DISMISS is able to confidently predict where DNA methylation predominates (plus or minus DNA strands – asymmetric DNA methylation; plus and minus DNA stands – symmetric DNA methylation) in MeDIP-Seq datasets derived from A. mellifera samples. When compared to DNA methylation data derived from BS-Seq analysis of A. mellifera worker larva, DISMISS-mediated identification of strand-specific methylated cytosines is 80 % accurate. Furthermore, DISMISS can correctly (p <0.0001) detect the origin (sense vs antisense DNA strands) of DNA methylation at splice site junctions in A. mellifera MeDIP-Seq datasets with a precision close to BS-Seq analysis. Finally, DISMISS-mediated identification of DNA methylation signals associated with upstream, exonic, intronic and downstream genomic loci from A. mellifera MeDIP-Seq datasets outperforms MACS2 (Model-based Analysis of ChIP-Seq2; a commonly used MeDIP-Seq analysis software) and closely approaches the results achieved by BS-Seq. CONCLUSIONS: While asymmetric DNA methylation is increasingly being found in growing numbers of eukaryotic species and is the predominant pattern observed in some invertebrate genomes, it has been difficult to detect in MeDIP-Seq datasets using existing software. DISMISS now enables more sensitive examinations of MeDIP-Seq datasets and will be especially useful for the study of genomes containing either low levels of DNA methylation or for genomes containing relatively high amounts of asymmetric methylation

Identifying and validating the presence of Guanine-Quadruplexes (G4) within the blood fluke parasite Schistosoma mansoni

Schistosomiasis is a neglected tropical disease that currently affects over 250 million individuals worldwide. In the absence of an immunoprophylactic vaccine and the recognition that mono-chemotherapeutic control of schistosomiasis by praziquantel has limitations, new strategies for managing disease burden are urgently needed. A better understanding of schistosome biology could identify previously undocumented areas suitable for the development of novel interventions. Here, for the first time, we detail the presence of G-quadruplexes (G4) and putative quadruplex forming sequences (PQS) within the Schistosoma mansoni genome. We find that G4 are present in both intragenic and intergenic regions of the seven autosomes as well as the sex-defining allosome pair. Amongst intragenic regions, G4 are particularly enriched in 3´ UTR regions. Gene Ontology (GO) term analysis evidenced significant G4 enrichment in the wnt signalling pathway (p<0.05) and PQS oligonucleotides synthetically derived from wnt-related genes resolve into parallel and anti-parallel G4 motifs as elucidated by circular dichroism (CD) spectroscopy. Finally, utilising a single chain anti-G4 antibody called BG4, we confirm the in situ presence of G4 within both adult female and male worm nuclei. These results collectively suggest that G4-targeted compounds could be tested as novel anthelmintic agents and highlights the possibility that G4-stabilizing molecules could be progressed as candidates for the treatment of schistosomiasi

The anti-fecundity effect of 5-azacytidine (5-AzaC) on Schistosoma mansoni is linked to dis-regulated transcription, translation and stem cell activities

Uncontrolled host immunological reactions directed against tissue-trapped eggs precipitate a potentially lethal, pathological cascade responsible for schistosomiasis. Blocking schistosome egg production, therefore, presents a strategy for simultaneously reducing immunopathology as well as limiting disease transmission in endemic or emerging areas. We recently demonstrated that the ribonucleoside analogue 5-azacytidine (5-AzaC) inhibited Schistosoma mansoni oviposition, egg maturation and ovarian development. While these anti-fecundity effects were associated with a loss of DNA methylation, other molecular processes affected by 5-AzaC were not examined at the time. By comparing the transcriptomes of 5-AzaC-treated females to controls, we provide evidence that this ribonucleoside analogue also modulates other crucial aspects of schistosome egg-laying biology. For example, S. mansoni gene products associated with amino acid-, carbohydrate-, fatty acid-, nucleotide- and tricarboxylic acid (TCA)- homeostasis are all dysregulated in 5-AzaC treated females. To validate the metabolic pathway most significantly affected by 5-AzaC, amino acid metabolism, nascent protein synthesis was subsequently quantified in adult schistosomes. Here, 5-AzaC inhibited this process by 68% ?16.7% (SEM) in male- and 81% ?4.8% (SEM) in female-schistosomes. Furthermore, the transcriptome data indicated that adult female stem cells were also affected by 5-AzaC. For instance, 40% of transcripts associated with proliferating schistosome cells were significantly down-regulated by 5-AzaC. This finding correlated with a considerable reduction (95%) in the number of 5-ethynyl-2?-deoxyuridine (EdU) positive cells found in 5-AzaC-treated females. In addition to protein coding genes, the effect that 5-AzaC had on repetitive element expression was also assessed. Here, 46 repeats were found differentially transcribed between 5-AzaC-treated and control females with long terminal repeat (LTR) and DNA transposon classes being amongst the most significant. This study demonstrates that the anti-fecundity activity of 5-AzaC affects more than just DNA methylation in schistosome parasites. Further characterisation of these processes may reveal novel targets for schistosomiasis controlauthorsversionPeer reviewe

Differential Brain Activation to Angry Faces by Elite Warfighters: Neural Processing Evidence for Enhanced Threat Detection

10.1371/journal.pone.0010096PLoS ONE54

The Structure of the {\beta} Leonis Debris Disk

We combine nulling interferometry at 10 {\mu}m using the MMT and Keck Telescopes with spectroscopy, imaging, and photometry from 3 to 100 {\mu}m using Spitzer to study the debris disk around {\beta} Leo over a broad range of spatial scales, corresponding to radii of 0.1 to ~100 AU. We have also measured the close binary star o Leo with both Keck and MMT interferometers to verify our procedures with these instruments. The {\beta} Leo debris system has a complex structure: 1.) relatively little material within 1 AU; 2.) an inner component with a color temperature of ~600 K, fitted by a dusty ring from about 2 to 3 AU; and 3.) a second component with a color temperature of ~120 K fitted by a broad dusty emission zone extending from about ~5 AU to ~55 AU. Unlike many other A-type stars with debris disks, {\beta} Leo lacks a dominant outer belt near 100 AU.Comment: 14 page body, 3 page appendix, 15 figure

Protein and small non-coding RNA-enriched extracellular vesicles are released by the pathogenic blood fluke Schistosoma mansoni

Background: Penetration of skin, migration through tissues and establishment of long-lived intravascular partners require Schistosoma parasites to successfully manipulate definitive host defences. While previous studies of larval schistosomula have postulated a function for excreted/secreted (E/S) products in initiating these host-modulatory events, the role of extracellular vesicles (EVs) has yet to be considered. Here, using preparatory ultracentrifugation as well as methodologies to globally analyse both proteins and small non-coding RNAs (sncRNAs), we conducted the first characterization of Schistosoma mansoni schistosomula EVs and their potential host-regulatory cargos. Results: Transmission electron microscopy analysis of EVs isolated from schistosomula in vitro cultures revealed the presence of numerous, 30–100 nm sized exosome-like vesicles. Proteomic analysis of these vesicles revealed a core set of 109 proteins, including homologs to those previously found enriched in other eukaryotic EVs, as well as hypothetical proteins of high abundance and currently unknown function. Characterization of E/S sncRNAs found within and outside of schistosomula EVs additionally identified the presence of potential gene-regulatory miRNAs (35 known and 170 potentially novel miRNAs) and tRNA-derived small RNAs (tsRNAs; nineteen 5′ tsRNAs and fourteen 3′ tsRNAs). Conclusions: The identification of S. mansoni EVs and the combinatorial protein/sncRNA characterization of their cargo signifies that an important new participant in the complex biology underpinning schistosome/host interactions has now been discovered. Further work defining the role of these schistosomula EVs and the function/stability of intra- and extra-vesicular sncRNA components presents tremendous opportunities for developing novel schistosomiasis diagnostics or interventions