Study and characterisation of the prodromal motor phase of Parkinson’s Disease

There is sufficient evidence that a neurodegenerative process in Parkinson’s Disease (PD) starts many years before the clinical diagnosis. The progression of PD is generally slow and, because it is diagnosed based on established motor features, it is probable that subtle motor manifestations appear in the pre-diagnostic phase of PD. Isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is a condition known to be part of the prodromal phase of PD. The PREDICT-PD study is a population-based cohort which aims to identify individuals at risk of PD based on the presence and absence of risk factors. The first project of this thesis investigated the association between first presentation of motor symptoms (tremor, rigidity and balance difficulties) and subsequent PD in a large primary care dataset in East London, including almost 3 decades of clinical information from over a million individuals. People who went on to develop PD reported motor symptoms up to 10 years before PD diagnosis. Tremor had the highest association with future PD followed by balance difficulties and rigidity. The second project aimed to identify the range of motor features in the elderly population participating in the PREDICT-PD cohort study and document their rate of progression over time. People classified as having a higher risk of future PD (using the PREDICT-PD algorithm) were more likely to have early parkinsonian signs than the lower risk group. Six years later, they also showed a bigger motor decline compared with people in the lower risk group. The third project was focused on developing two new objective motor tools, the Distal Finger Tapping test and the Slow-Motion Analysis of Repetitive Tapping. Both tests were able to detect abnormal patterns of movement amongst people with early PD. Finally, a motor battery was created and implemented in a group of patients with iRBD. A higher proportion of patients with iRBD had early parkinsonian signs compared with controls. The motor battery was able to detect early patterns of motor dysfunction not captured by standardised clinical scales. The work presented in this thesis demonstrates that motor features start in the pre-diagnostic phase of PD and describes new motor signatures in the prodromal phase of PD

Inactivation of Aspergillus niger spores from indoor air by photocatalytic filters

AIR:EAU+SPI:PRE:WHE:CGUThe effects of UV-A and UV-C radiation on fungal spores were investigated before and after their germination in photocatalytic and non-photocatalytic air filters commonly used in heating, ventilating, and air conditioning (HVAC) systems. Immediately after the coating of spores on filters, exposure to both types of UV radiation induced the appearance of an inactivation threshold for long durations of exposure probably resulting from the presence of Aspergillus niger spores inside the activated charcoal layer. The use of a thin photocatalytic filter without activated charcoal demonstrated a better disinfection efficiency with total inactivation of the spores, due to an optimal contact between spores and TiO2 coating. The effects of UV radiation were then assessed on spore germination for both types of filters. The inactivation of spores in illuminated photocatalytic filters resulted in an irreversible inhibition of the fungal germination under UV-A or UV-C radiation. In contrast, fungal spores were able to germinate in non-photocatalytic filters despite previous exposure to both types of UV radiation. The monitoring of ergosterol amounts, the major sterol of fungal membranes, corroborated these results. Finally, UV-A or UV-C radiation exposure of filters after spore germination had a lesser disinfection efficiency than experiments whereby spores had just been applied onto the filters, due to the absence of contact between the biological pollutants and the photocatalyst coating. Our results thus demonstrated the interest to use photocatalytic filters ensuring optimal contact between pollutants and TiO2 coating to lead to a total inactivation of fungal spores in filters of HVAC systems. (C) 2013 Elsevier B.V. All rights reserved

Efficiency of (photo)catalytic filters to remove bioaerosols : application to HVAC system

International @ EAU+CGU:FSIInternational audienceIndoor air quality has become a major public health concern and it potentially poses a threat to the health of all types of populations. Actually, populations in developed countries spend more than 80 % of their time in confined indoor environments. Indoor air pollutants emanate from various sources, chemical or biological. Most of the studies deal with the removal of chemical sources but biological treatment of indoor air remains an emerging research theme. Indeed, the removal of biological agents is a complex issue. None of the traditional technologies for indoor air decontamination, such as activated charcoal filters, HEPA filters with or without UV radiation, ozonation, air ionization, are completely effective. Moreover, these technologies still need further investigation. The aim is not only to trap the microorganisms present in the indoor air, but also to alter them irreversibly. In this context, the combination, within air treatment plants, of both the photocatalytic and the filtering process is a promising technology that would combine the benefits of both processes to efficiently trap and alter chemical and microbiological pollutants through total mineralisation. Our researches deals with the effects of UV-A and UV-C radiation on the coating of aerosolised cells of fungal spores before and after their germination but also on an experimental bioaerosol of bacteria in presence of photocatalytic and non-photocatalytic air filters commonly used in Heating, Ventilating, and Air Conditioning (HVAC) systems. E.coli and Aspergillus Niger are used as model of bacteria and fungi because E.coli is commonly used to evaluate indoor air cleaning technologies and A.Niger is known for its resistance to any environmental stress conditions, and especially the spores which contain a black fungal spore pigment, protecting them from UV radiation exposure. In presence of E.coli or A.Niger the photocatalytic filters without charcoal demonstrated better disinfection efficiency with full damages of the cells, probably resulting from an optimal contact between TiO2 coating and the microorganisms. In contrast, the use of filters with activated charcoal, even with UV-C, resulted in the apparition of an inactivation threshold that could be attributed to the penetration of cells within the activated charcoal layer and the absence of contact with the photocatalyst. However, UV-C photocatalysis was able to inactivate faster and, at the same time, mineralise biological pollutants than UV-A. In the case of A.Niger, the effects of UV radiation were also assessed on spore germination for both types of filters. The inactivation of spores in illuminated photocatalytic filters resulted in an irreversible inhibition of the fungal germination under UV-A or UV-C radiation. In contrast, fungal spores were able to germinate in non-photocatalytic filters despite previous exposure to both types of UV radiation. After spore germination disinfection efficiency is lower than experiments whereby spores had just been applied onto the filters, due to the absence of contact between the biological pollutants and the photocatalyst coating. Our results demonstrated the interest to use photocatalytic filters ensuring optimal contact between pollutants and TiO2 coating to lead to a total inactivation of fungal spores in filters of HVAC systems

An insight into the transcriptome of the digestive tract of the bloodsucking bug, Rhodnius prolixus.

The bloodsucking hemipteran Rhodnius prolixus is a vector of Chagas' disease, which affects 7-8 million people today in Latin America. In contrast to other hematophagous insects, the triatomine gut is compartmentalized into three segments that perform different functions during blood digestion. Here we report analysis of transcriptomes for each of the segments using pyrosequencing technology. Comparison of transcript frequency in digestive libraries with a whole-body library was used to evaluate expression levels. All classes of digestive enzymes were highly expressed, with a predominance of cysteine and aspartic proteinases, the latter showing a significant expansion through gene duplication. Although no protein digestion is known to occur in the anterior midgut (AM), protease transcripts were found, suggesting secretion as pro-enzymes, being possibly activated in the posterior midgut (PM). As expected, genes related to cytoskeleton, protein synthesis apparatus, protein traffic, and secretion were abundantly transcribed. Despite the absence of a chitinous peritrophic membrane in hemipterans - which have instead a lipidic perimicrovillar membrane lining over midgut epithelia - several gut-specific peritrophin transcripts were found, suggesting that these proteins perform functions other than being a structural component of the peritrophic membrane. Among immunity-related transcripts, while lysozymes and lectins were the most highly expressed, several genes belonging to the Toll pathway - found at low levels in the gut of most insects - were identified, contrasting with a low abundance of transcripts from IMD and STAT pathways. Analysis of transcripts related to lipid metabolism indicates that lipids play multiple roles, being a major energy source, a substrate for perimicrovillar membrane formation, and a source for hydrocarbons possibly to produce the wax layer of the hindgut. Transcripts related to amino acid metabolism showed an unanticipated priority for degradation of tyrosine, phenylalanine, and tryptophan. Analysis of transcripts related to signaling pathways suggested a role for MAP kinases, GTPases, and LKBP1/AMP kinases related to control of cell shape and polarity, possibly in connection with regulation of cell survival, response of pathogens and nutrients. Together, our findings present a new view of the triatomine digestive apparatus and will help us understand trypanosome interaction and allow insights into hemipteran metabolic adaptations to a blood-based diet.Journal ArticleResearch Support, N.I.H. IntramuralResearch Support, Non-U.S. Gov'tSCOPUS: ar.jSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Death to the bad buys: Targeting cancer via Apo2L/TRAIL

The original publication can be found at www.springerlink.comAll higher organisms consist of an ordered society of individual cells that must communicate to maintain and regulate their functions. This is achieved through a complex but highly regulated network of hormones, chemical mediators, chemokines and other cytokines, acting as ligands for intra or extra-cellular receptors. Ligands and receptors of the tumor necrosis factor (TNF) superfamilies are examples of signal transducers, whose integrated actions influence the development, homeostasis and adaptive responses of many cells and tissue types. Apo2L/TRAIL is one of several members of the tumour necrosis factor superfamily that induce apoptosis through the engagement of death receptors. Apo2L/TRAIL interacts with an unusually complex receptor system, which in humans comprises two death receptors and three decoy receptors. This molecule has received considerable attention recently because of the finding that many cancer cell types are sensitive to Apo2L/TRAIL-induced apoptosis, while most normal cells appear to be resistant to this action of Apo2L/TRAIL. In this review, we specifically emphasise on the actions of Apo2L/TRAIL with respect to its apoptotic signaling pathways and summarise what is known about its physiological role. The potential therapeutic usefulness of Apo2L/TRAIL, especially in combination with chemotherapeutic agents, is also discussed in some detail.S. Bouralexis, D. M. Findlay and A. Evdokio