Presymptomatic geographical distribution of ALS patients suggests the involvement of environmental factors in the disease pathogenesis

BackgroundGiven that the pathogenetic process of ALS begins many years prior to its clinical onset, examining patients' residential histories may offer insights on the disease risk factors. Here, we analyzed the spatial distribution of a large ALS cohort in the 50 years preceding the disease onset.MethodsData from the PARALS register were used. A spatial cluster analysis was performed at the time of disease onset and at 1-year intervals up to 50 years prior to that.ResultsA total of 1124 patients were included. The analysis revealed a higher-incidence cluster in a large area (435,000 inhabitants) west of Turin. From 9 to 2 years before their onset, 105 cases were expected and 150 were observed, resulting in a relative risk of 1.49 (P = 0.04). We also found a surprising high number of patients pairs (51) and trios (3) who lived in the same dwelling while not being related. Noticeably, these occurrences were not observed in large dwellings as we would have expected. The probability of this occurring in smaller buildings only by chance was very low (P = 0.01 and P = 0.04 for pairs and trios, respectively).ConclusionsWe identified a higher-incidence ALS cluster in the years preceding the disease onset. The cluster area being densely populated, many exposures could have contributed to the high incidence ALS cluster, while we could not find a shared exposure among the dwellings where multiple patients had lived. However, these findings support that exogenous factors are likely involved in the ALS pathogenesis

Structural and Functional Characterization of Hermetia illucens Larval Midgut

The larvae of Hermetia illucens are among the most promising agents for the bioconversion of low-quality biomass, such as organic waste, into sustainable and nutritionally valuable proteins for the production of animal feed. Despite the great interest in this insect, the current literature provides information limited to the optimization of rearing methods for H. illucens larvae, with particular focus on their efficiency in transforming different types of waste and their nutritional composition in terms of suitability for feed production. Surprisingly, H. illucens biology has been neglected and a deep understanding of the morphofunctional properties of the larval midgut, the key organ that determines the extraordinary dietary plasticity of this insect, has been completely overlooked. The present study aims to fill this gap of knowledge. Our results demonstrate that the larval midgut is composed of distinct anatomical regions with different luminal pH and specific morphofunctional features. The midgut epithelium is formed by different cell types that are involved in nutrient digestion and absorption, acidification of the lumen of the middle region, endocrine regulation, and growth of the epithelium. A detailed characterization of the activity of enzymes involved in nutrient digestion and their mRNA expression levels reveals that protein, carbohydrate, and lipid digestion is associated to specific regions of this organ. Moreover, a significant lysozyme activity in the lumen of the anterior and middle regions of the midgut was detected. This enzyme, together with the strong acidic luminal pH of middle tract, may play an important role in killing pathogenic microorganisms ingested with the feeding substrate. The evidence collected led us to propose a detailed functional model of the larval midgut of H. illucens in which each region is characterized by peculiar features to accomplish specific functions. This platform of knowledge sets the stage for developing rearing protocols to optimize the bioconversion ability of this insect and its biotechnological applications.The larvae of Hermetia illucens are among the most promising agents for the bioconversion of low-quality biomass, such as organic waste, into sustainable and nutritionally valuable proteins for the production of animal feed. Despite the great interest in this insect, the current literature provides information limited to the optimization of rearing methods for H. illucens larvae, with particular focus on their efficiency in transforming different types of waste and their nutritional composition in terms of suitability for feed production. Surprisingly, H. illucens biology has been neglected and a deep understanding of the morphofunctional properties of the larval midgut, the key organ that determines the extraordinary dietary plasticity of this insect, has been completely overlooked. The present study aims to fill this gap of knowledge. Our results demonstrate that the larval midgut is composed of distinct anatomical regions with different luminal pH and specific morphofunctional features. The midgut epithelium is formed by different cell types that are involved in nutrient digestion and absorption, acidification of the lumen of the middle region, endocrine regulation, and growth of the epithelium. A detailed characterization of the activity of enzymes involved in nutrient digestion and their mRNA expression levels reveals that protein, carbohydrate, and lipid digestion is associated to specific regions of this organ. Moreover, a significant lysozyme activity in the lumen of the anterior and middle regions of the midgut was detected. This enzyme, together with the strong acidic luminal pH of middle tract, may play an important role in killing pathogenic microorganisms ingested with the feeding substrate. The evidence collected led us to propose a detailed functional model of the larval midgut of H. illucens in which each region is characterized by peculiar features to accomplish specific functions. This platform of knowledge sets the stage for developing rearing protocols to optimize the bioconversion ability of this insect and its biotechnological applications

The killer yeast Wickerhamomyces anomalus associated to the sand fly Phlebotomus perniciosus: possible implication against the pathogen Leishmania spp.

While arthropod-associated bacteria are the focus of several research programs aimed at developing strategies to control vector-borne diseases, such as malaria, dengue, and trypanosomiasis, arthropod-associated yeasts and their killer toxins have not yet been deeply investigated. I focused my work on the sand fly\ua0Phlebotomus perniciosus, the main vector of human and canine leishmaniasis in the western Mediterranean area, with the aim of investigating if a yeast associated with this arthropod could exert inhibitory/killing activity against the pathogen Leishmania spp. We isolated and phylogenetically characterized strains of the yeast\ua0species Wickerhamomyces anomalus, from laboratory-reared adults and larvae of P. perniciosus. The yeast W. anomalus is renowned for its potential in biocontrol and has been isolated from different substrates and habitats including several mosquito species, in witch it showed the ability to produce a killer toxin active against other yeast species. In the present research, the isolated yeast strains of the species W. anomalus were tested against sensitive yeast strains, demonstrating its killer phenotype. Finally, in order to explore the possibility that this yeast could exert inhibitory/killing activity against pathogens, I tested the in vitro activity of W. anomalus strains against Leishmania infantum. This study offers the basis for the development of a method for vector-borne disease control that is environment-friendly and safe for human health. The use of yeast symbionts with antimicrobial proprieties could be included in the integrated approach for the control of leishmaniases, a worldwide re-emerging public health problem

Characterization of fungal symbiosis in phlebotomus perniciosus and evaluation of its possible implications for the control of Leishmaniases

The control of vector-borne diseases represents one of the greatest global public health challenges of the 21st century. In this context, biological control methods are an alternative to the use of chemicals, and the use of microorganisms is now well established in biocontrol. While arthropod-associated bacteria are the focus of several research programs aimed at developing strategies to control vector-borne diseases, such as malaria, dengue, and trypanosomiasis, arthropod-associated yeasts and their killer toxins have not yet been deeply investigated. In this work, we studied the yeast community associated with the sand fly Phlebotomus perniciosus, the main vector of leishmaniasis in the western Mediterranean area, with the aim of investigating their potential to interfere with Leishmania development in the insect. To reach the goal we associated culture-based methodology with culture independent methods: we performed yeast isolation and identification, 454 Pyrosequencing, PCR screening and whole mount FISH with specific probes to localize the yeast species. We focused our attention to the yeast Wickerhamomyces anomalus, isolated from both sexes of P. perniciosus; this yeast was phylogenetically characterized and tested against sensitive yeast strains, demonstrating its killer phenotype. Finally, in order to explore the possibility that this yeast could exert inhibitory/killing activity against pathogens, we tested the in vitro activity of W. anomalus strains against Leishmania infantum. This study offers the basis for the development of a method for vector-borne disease control that is environment-friendly and safe for human health. The use of yeast symbionts with antimicrobial proprieties could be included in the integrated approach for the control of leishmaniases, a worldwide re-emerging public health problem

Yeast symbionts in Phlebotomus perniciosus: possible implications for the control of vector-borne diseases

The control of vector-borne diseases represents one of the greatest global public health challenges of the 21st century. In this context, biological control methods represent an alternative to the use of chemicals, and the use of microorganisms is now well established in biocontrol. While arthropod-associated bacteria are the focus of several research programs aimed at developing strategies to control vector-borne diseases, such as malaria, dengue, and trypanosomiasis, arthropod-associated yeasts and their killer toxins have not yet been deeply investigated. We present our studies, conducted with culture-based and culture independent methods (454 Pyrosequencing, PCR screening, FISH), on the yeast community associated with the sand fly Phlebotomus perniciosus, the main vector of leishmaniases in the western Mediterranean area, with the aim of investigating their potential to interfere with Leishmania development in the insect. As one of the results, we isolated and phylogenetically characterized a strain of the yeast Wickerhamomyces anomalus with killer phenotype from laboratory-reared sand flies. The association between P. perniciosus and yeasts deserves to be further investigated, in order to explore the possibility that this yeast could exert inhibitory/killing activity against Leishmania spp

Hybrid membranes based on sulfated titania nanoparticles as low-cost proton conductors

This work reports on a novel, hybrid solid-state membrane based on sulfated titania nanoparticles stabilized by a polyvinylidene fluoride-hexafluoropropylene copolymer. A fast solvent-casting technique was adopted as a valid alternative to a fully dry, hot-pressing preparation procedure. Self-standing, flexible membranes with high proton conductivity were obtained