Prion pathogenesis and secondary lymphoid organs (SLO): Tracking the SLO spread of prions to the brain

Prion diseases are subacute neurodegenerative diseases that affect humans and a range of domestic and free-ranging animal species. These diseases are characterized by the accumulation of PrP(Sc), an abnormally folded isoform of the cellular prion protein (PrP(C)), in affected tissues. The pathology during prion disease appears to occur almost exclusively within the central nervous system. The extensive neurodegeneration which occurs ultimately leads to the death of the host. An intriguing feature of the prion diseases, when compared with other protein-misfolding diseases, is their transmissibility. Following peripheral exposure, some prion diseases accumulate to high levels within lymphoid tissues. The replication of prions within lymphoid tissue has been shown to be important for the efficient spread of disease to the brain. This article describes recent progress in our understanding of the cellular mechanisms that influence the propagation of prions from peripheral sites of exposure (such as the lumen of the intestine) to the brain. A thorough understanding of these events will lead to the identification of important targets for therapeutic intervention, or alternatively, reveal additional processes that influence disease susceptibility to peripherally-acquired prion diseases

Comparison of porcine thorax to gelatine blocks for wound

Published online first in International Journal of Legal Medicine. The support of EPSRC and The Home Office are recognised. Open Access, this article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:/ /creativecommons.org/licenses/by/4.0/)Tissue simulants are typically used in ballistic testing as substitutes for biological tissues. Many simulants have been used, with gelatine amongst the most common. While two concentrations of gelatine (10 and 20 %) have been used extensively, no agreed standard exists for the preparation of either. Comparison of ballistic damage produced in both concentrations is lacking. The damage produced in gelatine is also questioned, with regards to what it would mean for specific areas of living tissue. The aim of the work discussed in this paper was to consider how damage caused by selected pistol and rifle ammunition varied in different simulants. Damage to gelatine blocks 10 and 20 % in concentration were tested with 9 mm Luger (9 × 19 full metal jacket; FMJ) rounds, while damage produced by .223 Remington (5.56 × 45 Federal Premium® Tactical® Bonded®) rounds to porcine thorax sections (skin, underlying tissue, ribs, lungs, ribs, underlying tissue, skin; backed by a block of 10 % gelatine) were compared to 10 and 20 % gelatine blocks. Results from the .223 Remington rifle round, which is one that typically expands on impact, revealed depths of penetration in the thorax arrangement were significantly different to 20 % gelatine, but not 10 % gelatine. The level of damage produced in the simulated thoraxes was smaller in scale to that witnessed in both gelatine concentrations,though greater debris was produced in the thoraxes.The support of EPSRC and The Home Office are recognised

The overmatching of UK police body armour

Police officers and other personnel in the UK routinely wear body armour that provides protection from specific threats. Typically, 'soft' armours, usually formed from multiple layers of fabric, can protect wearers from fragmentation and low velocity (handgun) ballistic threats, while ‘hard’ armours, formed from ceramic and composite plates, offer protection from high velocity (rifle) threats. Protection from stab and/or slash attack is predominantly provided by utilising chain mail and laminated solutions. The question has been raised however, of what would happen when armour is overmatched with a greater threat than it is designed to protect against. A limited number of studies have been published in the open source literature regarding the overmatching of soft body armour. This research aims to increase the understanding of overmatching, by investigating the effect of both i) soft fabric body armour designed to protect from handgun ammunition being challenged by high velocity rifle projectiles and ii) knife and spike resistant armour protecting against low velocity handgun projectiles. A subsection of the research considered three tissue simulants in order to find the most suitable for investigating the effects of overmatching armour. A method for recording the damage produced in the simulants was also developed; from which comparison of damage to different targets was possible. Following the tissue simulant investigation, gelatine blocks 10% in concentration were selected and used to investigate the overmatching of two types of UK police body armour. Three different arrangements were setup, namely 10% gelatine blocks 500mm, 10% gelatine blocks 250mm in length, and porcine thoracic walls arranged to simulate a thorax. Testing blocks 500mm in length was a set-up typical to ballistic investigations; the blocks were capable of capturing the majority of the projectiles’ damage, with the damage produced in both unprotected and protected (on the front face only) targets compared. Based on anthropometric measurements, testing 10% gelatine blocks 250mm in size was more representative of a torso sized target. With the blocks smaller, armour was placed on both the front and back face of targets. This is more representative of how armour would be worn in a real life scenario; patrolling UK police officer wearing armour that protects both the front and back of their torso. Finally, the use of porcine samples arranged to simulate both protected and unprotected thoraxes enabled comparisons of the damage seen in homogenous tissue simulants to damage in non-homogenous material typical to those found in the human torso. The outcomes from testing three different targets with two ammunition and armour combinations revealed the effect of overmatching armour is not one that can be generalised and predicted for all overmatching scenarios. The presence of armour on the rear face of targets based on typical measurements of human chest depth, increased the chances of the projectiles tested remaining within the targets.EPSR

tuppence-based SERS for the detection of illicit materials

Deposition of silver onto British 2p coins has been demonstrated as an efficient and cost effective approach to producing substrates capable of promoting surface enhanced Raman scattering (SERS). Silver application to the copper coins is undemanding taking just 20 s, and results in the formation of multiple hierarchial dendritic structures. To demonstrate that the silver deposition sites were capable of SERS the highly fluorescent Rhodamine 6G (R6G) probe was used. Analyses indicated that Raman enhancement only occurs at the silver deposition sites and not from the roughened copper surface. The robustness of the substrate in the identification and discrimination of illegal and legal drugs of abuse was then explored. Application of the drugs to the substrates was carried out using spotting and soaking methodologies. Whilst little or no SERS spectra of the drugs were generated upon spotting, soaking of the substrate in a methanolic solution of the drugs yielded a vast amount of spectral information. Excellent reproducibility of the SERS method and classification of three of the drugs, 4-methylmethcathinone (mephedrone), 5,6-methylenedioxy-2-aminoindane (MDAI) and 3,4-methylenedioxy-N-methylamphetamine (MDMA) were demonstrated using principal components analysis and partial least squares

Microfold (M) cells: important immunosurveillance posts in the intestinal epithelium

This article suggest that technopreneurship subject should no longer be offered to ITB student as an optional subject but a compulsory one. The reason is that this subject may enable ITB's graduates to be technopreneurs when they graduate. In his opinion, a technopreneur is regarded as a critical success factor in increasing both Growth National Product (GNP). Therefore, their role in resolving Indonesia's current multi dimensional crises and enhancing Indonesia's development will be very significant. The writer also claims that this subject is relevant for ITB's student-who will become engineers and specialists in arts when they graduate-since technopreneurship subject teaches the students how to do business in the field of engineering and art and train the students to acquire technopreneur's qualities such as being critical, innovative, reasonable, positive thinking, risk taking person

Microglia deficiency accelerates prion disease but does not enhance prion accumulation in the brain: Microglia and prion disease

Prion diseases are transmissible, neurodegenerative disorders associated with misfolding of the prion protein. Previous studies show that reduction of microglia accelerates central nervous system (CNS) prion disease and increases the accumulation of prions in the brain, suggesting that microglia provide neuroprotection by phagocytosing and destroying prions. In Csf1r (ΔFIRE) mice, the deletion of an enhancer within Csf1r specifically blocks microglia development, however, their brains develop normally and show none of the deficits reported in other microglia‐deficient models. Csf1r (ΔFIRE) mice were used as a refined model in which to study the impact of microglia‐deficiency on CNS prion disease. Although Csf1r (ΔFIRE) mice succumbed to CNS prion disease much earlier than wild‐type mice, the accumulation of prions in their brains was reduced. Instead, astrocytes displayed earlier, non‐polarized reactive activation with enhanced phagocytosis of neuronal contents and unfolded protein responses. Our data suggest that rather than simply phagocytosing and destroying prions, the microglia instead provide host‐protection during CNS prion disease and restrict the harmful activities of reactive astrocytes