Characterization, cloning and immunogenicity of antigens released by lung-stage larvae of Schistosoma mansoni

Lung-stage schistosomula are the target of protective immunity in mice vaccinated with attenuated cercariae of Schistosoma mansoni. Therefore, proteins present at this developmental stage, and in particular those which are secreted, are a potential source of novel vaccine candidates. However, little information is available about such molecules. Here we describe the cDNA clones identified by screening expression libraries with serum raised against proteins released by lung-stage schistosomula. In total, 11 different cDNA species were identified, 6 of which have been described previously in S. mansoni; these included fructose 1,6-bisphosphate aldolase and Sm21.7 which together accounted for two-thirds of all positive clones. Of the 5 newly described schistosome genes, 1 cDNA had a high degree of homology to the s5a subunit of 26S proteasomes, most significant being with the human protein. The remaining 4 clones showed no significant homologies to any genes sequenced previously. Fructose 1,6-bisphosphate aldolase, Sm21.7, the proteasome homologue and 1 unknown clone (A26) have been expressed in a bacterial expression system and serum produced against each recombinant protein. Immunolocalization showed fructose 1,6-bisphosphate aldolase, Sm21.7 and the proteasome homologue to be most abundant in muscle cells whilst clone A26 was distributed throughout many tissues, but was most abundant in the tegument. Analysis of the cellular immune responses of vaccinated mice showed 3 of the 4 expressed clones to be highly immunogenic, inducing the secretion of large quantities of the Th1-type cytokine interferon gamma

Carbon Nitride as a Ligand: Synthesis, Characterisation and Application

Carbon nitride’s properties can be tuned through the coordination of metal atoms, which can lead to enhanced catalytic activity. However, to date, there are few reported examples of inner-sphere coordination of metal complex fragments to carbon nitride. Therefore, the effects of coordination of metal complex fragments to carbon nitride haves been investigated. Reaction of the rhenium carbonyl complex, [ReCl(CO)5] with the surface of urea-derived carbon nitride (UCN) results in [ReCl(CO)3(UCN)], with a rhenium concentration of 0.39 mmol g-1. The synthesis of the manganese analogue resulted in manganese oxidation leading to [Mn(UCN)] ([Mn] = 0.24 mmol g-1). Infrared spectroscopy, along with crystal structures of molecular analogues, [MCl(CO)3(DMNA-κ2N, N’)] (M = Re, Mn) was used to gain insight into the coordination of metals complex fragments to carbon nitride. Two morphologies of carbon nitride, unstructured urea-derived carbon nitride (UCN) and porous cyanamide derived carbon nitride (CCN), were then decorated with [Ru(bpy)2]2+ fragments. The carbon nitride structure affected metal loading, as [Ru(bpy)2(UCN)](PF6)2 ([Ru] = 0.016 mmol g-1) showed lower metal loading compared to [Ru(bpy)2(CCN)](PF6)2 ([Ru] = 0.076 mmol g-1). [Ru(bpy)2(DMNA-κ2N, N’)](PF6)2 was synthesised as a molecular analogue to gain insight into the coordination mode. The photocatalytic activities of [Ru(bpy)2(UCN)](PF6)2 and [Ru(bpy)2(UCN)](PF6)2 were completely inhibited compared to the undecorated materials. EPR and photoluminescence suggested the presence of rapid, efficient quenching of excited states in ruthenium decorated carbon nitride. [IrCl2Cp*(UCN)] ([Ir] = 0.069 mmol g-1) was synthesised to design a novel, recyclable hydrogenation catalyst. Direct hydrogenation reactions were carried out using hexane as a solvent, and despite low activity, [IrCl2Cp*(UCN)] showed good selectivity toward terminal alkenes and over 80% of catalytic activity was retained after 5 catalytic runs. Direct coordination of metal complex fragments to carbon nitride is shown to be a viable route to tuning the properties of carbon nitride and developing recyclable novel catalysts

A sensory-guided surgical micro-drill

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 The Authors.This article describes a surgical robotic device that is able to discriminate tissue interfaces and other controlling parameters ahead of the drill tip. The advantage in such a surgery is that the tissues at the interfaces can be preserved. A smart tool detects ahead of the tool point and is able to control the interaction with respect to the flexing tissue, to avoid penetration or to control the extent of protrusion with respect to the position of the tissue. For surgical procedures, where precision is required, the tool offers significant benefit. To interpret the drilling conditions and the conditions leading up to breakthrough at a tissue interface, a sensing scheme is used that discriminates between the variety of conditions posed in the drilling environment. The result is a fully autonomous system, which is able to respond to the tissue type, behaviour, and deflection in real-time. The system is also robust in terms of disturbances encountered in the operating theatre. The device is pragmatic. It is intuitive to use, efficient to set up, and uses standard drill bits. The micro-drill, which has been used to prepare cochleostomies in the theatre, was used to remove the bone tissue leaving the endosteal membrane intact. This has enabled the preservation of sterility and the drilling debris to be removed prior to the insertion of the electrode. It is expected that this technique will promote the preservation of hearing and reduce the possibility of complications. The article describes the device (including simulated drill progress and hardware set-up) and the stages leading up to its use in the theatre.Queen Elizabeth Hospital, Birmingham, U

Feasibility study of a hand guided robotic drill for cochleostomy

The concept of a hand guided robotic drill has been inspired by an automated, arm supported robotic drill recently applied in clinical practice to produce cochleostomies without penetrating the endosteum ready for inserting cochlear electrodes. The smart tactile sensing scheme within the drill enables precise control of the state of interaction between tissues and tools in real-time. This paper reports development studies of the hand guided robotic drill where the same consistent outcomes, augmentation of surgeon control and skill, and similar reduction of induced disturbances on the hearing organ are achieved. The device operates with differing presentation of tissues resulting from variation in anatomy and demonstrates the ability to control or avoid penetration of tissue layers as required and to respond to intended rather than involuntary motion of the surgeon operator. The advantage of hand guided over an arm supported system is that it offers flexibility in adjusting the drilling trajectory. This can be important to initiate cutting on a hard convex tissue surface without slipping and then to proceed on the desired trajectory after cutting has commenced. The results for trials on phantoms show that drill unit compliance is an important factor in the design

The relationship between alexithymia and self-harm: the mediating role of mindfulness

Objectives. Self-harm, defined as any act of self-injury, irrespective of motivation, is a phenomenon which can have serious consequences for the individual, as well as significant public health costs. Many correlational studies have established a significant association between self-harm and alexithymia, a cognitive deficit in emotion processing, characterised by a difficulty identifying and describing feelings and an externally orientated thinking style. The current study investigated whether this relationship is explained by low levels of dispositional mindfulness. Methods. An opportunity sample of 325 community-based adults completed an online survey measuring their history of self-harm, alexithymia (Toronto Alexithymia Scale) and mindfulness (Five Facets of Mindfulness Questionnaire). Results. Alexithymia was significantly higher among participants with a history of self-harm, compared with participants with no history of self-harm. All mindfulness facets were significantly lower among participants with a history of self-harm except the facet Observe which was significantly higher in that group. A multiple mediation analysis found that the mindfulness facets Non-judge and Non-react were positive, significant mediators of the relationship between alexithymia and self-harm, but the facet Observe suppressed the relationship. Conclusions. The relationship between alexithymia and self-harm can be explained in part by deficits in mindfulness skills, particularly the ability to accept emotional experience without judgment or reaction. Conversely, the external orientation of alexithymia may itself be protective against self-harm, through the avoidance of excessive introspection. Thus, merely learning to observe inner experience, without the ability to understand and accept that experience, may have adverse consequences