Differential spatial repositioning of activated genes in Biomphalaria glabrata snails infected with Schistosoma mansoni

Copyright @ 2014 Arican-Goktas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Schistosomiasis is an infectious disease infecting mammals as the definitive host and fresh water snails as the intermediate host. Understanding the molecular and biochemical relationship between the causative schistosome parasite and its hosts will be key to understanding and ultimately treating and/or eradicating the disease. There is increasing evidence that pathogens that have co-evolved with their hosts can manipulate their hosts' behaviour at various levels to augment an infection. Bacteria, for example, can induce beneficial chromatin remodelling of the host genome. We have previously shown in vitro that Biomphalaria glabrata embryonic cells co-cultured with schistosome miracidia display genes changing their nuclear location and becoming up-regulated. This also happens in vivo in live intact snails, where early exposure to miracidia also elicits non-random repositioning of genes. We reveal differences in the nuclear repositioning between the response of parasite susceptible snails as compared to resistant snails and with normal or live, attenuated parasites. Interestingly, the stress response gene heat shock protein (Hsp) 70 is only repositioned and then up-regulated in susceptible snails with the normal parasite. This movement and change in gene expression seems to be controlled by the parasite. Other differences in the behaviour of genes support the view that some genes are responding to tissue damage, for example the ferritin genes move and are up-regulated whether the snails are either susceptible or resistant and upon exposure to either normal or attenuated parasite. This is the first time host genome reorganisation has been seen in a parasitic host and only the second time for any pathogen. We believe that the parasite elicits a spatio-epigenetic reorganisation of the host genome to induce favourable gene expression for itself and this might represent a fundamental mechanism present in the human host infected with schistosome cercariae as well as in other host-pathogen relationships.NIH and Sandler Borroughs Wellcome Travel Fellowshi

La contribution de l'épigénétique dans l'expression des variants phénotypiques essentiels pour l'interaction : Schistosoma mansoni / Biomphalaria glabrata

Phenotypic variability is defined as the capacity of a given population to produce phenotypic variants under theinfluence of the environment. Some of the phenotypic variants are heritable. It is generally assumed that thegenetic variations are the sole source of heritable phenotypic variants. However, recent studies have shown thatepigenetic variations can provide alternative source for phenotypic variants without change in DNA sequence. Inhost / parasite interactions, parasites impose selective pressures on their hosts and vice versa, leading to a genuinearms race between both partners. Such interaction leads to rapid adaptation where each partner has to evolve thecapacity to express new phenotypic variants. We propose that epigenetic variations play an important role in thegenesis of phenotypic variability. Schistosoma mansoni is a human parasite that causes intestinal schistosomiasis.During the PhD project, I was interested in the interaction of S. mansoni with its intermediate host Biomphalariaglabrata. The two main goals of this PhD project were: (i) To determine the relative weight of epigenetics andgenetics in the expression of phenotypic variants in the parasite. (ii) To initiate the investigation of epigeneticmechanisms in the host.The results show that histone modifications i.e. changes in the epigenetic information are indeed a source ofphenotypic variants in S. mansoni. These phenotypic variants confer a higher fitness to the parasite, by increasingits compatibility towards the mollusk. Finally, studying the heritability of epigenetic changes showed a nonmendeliansegregation. For B. glabrata, I was the first to show the DNA methylation in the snail. 2% of totalcytosines are methylated in his genome.La variabilité phénotypique est définie comme la capacité d’une espèce donnée à produire des variantsphénotypique à partir d’un seul génotype, sous l’influence de l’environnement. Certains de ces variants sonthéritables. L’origine de la variabilité phénotypique a toujours constitué un grand débat parmi les scientifiques.Jusqu’à récemment, il était communément accepté que la diversité génétique soit la seule source de variabilitéphénotypique. Cependant, les études récentes montrent que des variations épigénétiques pourraient être unesource alternative pour les variants phénotypiques, sans modifier la séquence de l’ADN. Dans les interactionshôte / parasite, les parasites exercent des pressions sélectives sur leurs hôtes et vice versa, conduisant à unevéritable course aux armements entre les deux partenaires. Une telle interaction nécessite une adaptation rapideoù chaque partenaire doit présenter la capacité d’exprimer de nouveaux variants phénotypiques. Nous proposonsque des variations épigénétiques puissent jouer un rôle important dans la genèse de la variabilité phénotypique.Schistosoma mansoni est un parasite humain responsable de la bilharziose intestinale. Au cours de la thèse, nousnous sommes intéressés à l’interaction du parasite S. mansoni avec son hôte intermédiaire le mollusqueBiomphalaria glabrata. Les deux principaux objectifs de cette thèse ont été de : (i) Déterminer le poids relatif del’épigénétique et de la génétique dans l’expression des variants phénotypiques chez le parasite. (ii) Initier lestravaux de recherche sur les mécanismes épigénétiques existant chez le mollusque hôte.Les résultats de nos travaux ont montré que les structures chromatiniennes via des modifications posttraductionnellesdes histones contribuent à modifier la variabilité phénotypique chez S. mansoni. Par ailleurs,nous avons montré que les variants phénotypiques générés confèrent au parasite une meilleure fitness. Cettedernière a été traduite par l’augmentation de sa compatibilité vis-à-vis de B. glabrata. Finalement, l’étude del’héritabilité des modifications épigénétiques a montré une transmission non mendélienne. En ce qui concerne B.glabrata, nous avons été les premiers à mettre en évidence la méthylation de l’ADN chez ce mollusque. Au niveaude son génome, 2% des cytosines totales sont méthylées

Frequency Analysis and Applications

The goal of this thesis is to study signals that have a regularity property defined in the frequency space, such as a decay on average of the amplitude of their Fourier transform, by using techniques from frequency analysis. Frequency analysis is a set of techniques that involve an analysis in the Fourier domain. We review some of these techniques and some principles. More precisely we will decompose a signal into countable sums of functions of which the Fourier transform is compactly supported in a ball or an annulus by performing a Littlewood–Paley decomposition. We will apply this technique to study the properties of functions having a specific regularity. Over two hundred years ago, Fourier studied problems related to the series expansions of periodic signals using elementary trigonometric polynomials. The theory was extended to non-periodic signals by using the Fourier transform and forms the core of harmonic analysis. Harmonic analysis is used in various fields such as signal processing and partial differential equations (PDEs)

Psychosocial determinants of intention to seek palliative care among the public in lebanon: A cross-sectional study

Objectives: This study aimed to assess the psychosocial determinants of intention to seek palliative care for the client themselves, or intention to enroll a family member in palliative care among the public in Lebanon. Methods: A cross-sectional study was initiated in 2020 on a convenience sample of adults permanently living in the Greater Beirut (GB) area; people with no current or previous experience with palliative care either for themselves or for someone dear to them were included. Verbal consent was obtained before data collection, and participants received a questionnaire to be self-completed, statistical analysis was performed using SPSS statistics version 23.0. Results: A total of 875 participants with a mean age of 42 years were interviewed, of whom 24 participants (2.7%) had had a previous experience with PC, either personally or with someone very close to them. The best-fit multivariate predictive model for intention to use PC included older age, positive attitude, and higher perceived control on one’s health. The multivariate model for intention to recommend use was significantly associated with a positive attitude, higher perceived control, and lower perceived barriers. Conclusions: Promotional activities should be conducted to provide the Lebanese public with accurate, detailed, and direct information about the benefits of PC, involving essentially physicians. Future research should explore the decision-making process in “real-time” situations, and within our specific psychosocial, cultural, and organizational context. © The Author(s) 2022

Faire du sur-place sans jamais pouvoir prendre place : l’interminable arrivée de jeunes maghrébins sans-papiers à Genève

Cet article analyse l’expérience de jeunes maghrébins nouvellement arrivés à Genève. Précarisés par leur parcours d’errance, sans statut légal, ils trouvent à Genève une infrastructure d’accueil qui leur permet de se nourrir et de dormir au chaud. Cependant, cette hospitalité a un coût : elle leur demande de suivre un parcours quotidien déterminé et rythmé par les services délivrés à heures fixes dans différents lieux d’accueil. Ce mode de vie combine mobilité et immobilité, donnant aux nouveaux arrivants l’impression de faire du surplace. Ceux-ci s’aménagent alors des échappatoires, notamment dans des conduites délictuelles, mais trouvent rarement d’autre issue que de reprendre la route. Nous analyserons ici les caractéristiques de cette hospitalité particulière à travers quatre épreuves qu’ils rencontrent : se familiariser, habiter, gagner sa vie et se projeter. Ce qui rend ces épreuves souvent insurmontables tient tant dans l’orientation et l’organisation de l’infrastructure d’accueil que dans la situation spécifique de ce groupe de jeunes sans-papiers.This article focuses on the experience of young North Africans newcomers in Geneva. Precarised by their wandering and lacking legal status, they find in Geneva a reception infrastructure that allows them to eat and sleep in warm place. However, this hospitality comes at a price: they are forced to follow a set daily routine, determined by the services provided at set times in different reception centres. This way of life combines mobility and immobility, giving the newcomers the impression of being stuck in motion. They then develop escape strategies, notably criminal behaviour, but rarely find any other way out than to go back on the road. Here we analyse the characteristics of this particular hospitality through four trials that they encounter: getting familiar, dwelling, earning a living, and making plans. What makes these trials often insurmountable is both the orientation and organisation of the reception infrastructure and the specific situation of this group of young undocumented migrants.Este artículo analiza la experiencia de varios jóvenes norteafricanos recientemente llegados a Ginebra. En precariedad debido a su trayectoria errante y a la falta de estatus legal, encuentran en Ginebra una infraestructura de acogida que les permite comer y dormir abrigados. Sin embargo, esta hospitalidad tiene un coste: les obliga a seguir una rutina diaria establecida y marcada por los servicios ofrecidos a la misma hora en distintos centros de acogida. Este modo de vida combina la movilidad y la inmovilidad, les da la impresión de quedarse atascados. Descubren formas de salir, sobre todo a través de comportamientos delictivos, pero rara vez encuentran otra salida que retomar el camino. A continuación, analizaremos las características de esta particular hospitalidad a través de cuatro situaciones que se les presentan: relacionarse, vivir, ganarse la vida y hacer planes. Analizaremos las características de esta particular hospitalidad a través de cuatro situaciones que se les presentan: familiarizarse, habitar, ganarse la vida y planificar. El hecho de que estas pruebas sean a menudo insuperables radica tanto en la orientación y la organización de las infraestructuras de acogida como en la situación específica de este grupo de jóvenes indocumentados

Social Workers and Irregular Migrants in the Assistance Circuit: Making Sense of Paradoxical Inclusion

Despite restrictive policy frameworks, cities sometimes provide support to irregular migrants. Scholars have analysed these forms of inclusion, focusing on policies and tensions between inclusionary approaches by local or urban actors and exclusionary approaches by national or supranational authorities. This article seeks to shift the focus to the street level, examining how support is delivered, how it is experienced by different categories of irregular migrants, and how frontline social workers make sense of their work and foster “paradoxical inclusion.” To this end, the article first analyses the experiences of young North African irregular migrants in Geneva, Switzerland. Based on ethnographic research, we describe their everyday life in the “assistance circuit,” which forces them to follow a daily routine determined by the services offered at fixed times in different places. Over time, the young men develop a sense of entrapment and alienation, as well as escape strategies. Secondly, by examining the perspective of social workers, we show that the constraints associated with the assistance circuit reflect a social work paradigm that aims to keep people on the move, limit dependency and promote autonomy. This paradigm coexists with another, conflicting one, which can be described as palliative, but which also seems paradoxical to the irregular migrants who aspire to full participation in social and economic life. Overall, our study suggests an alternative interpretation of the limitations and paradoxes surrounding irregular migrants’ inclusion that complements policy‐oriented approaches

Effect of cadmium on cytosine hydroxymethylation in gastropod hepatopancreas

5-Hydroxymethylcytosine (5hmC) is an important, yet poorly understood epigenetic DNA modification, especially in invertebrates. Aberrant genome-wide 5hmC levels have been associated with cadmium (Cd) exposure in humans, but such information is lacking for invertebrate bioindicators. Here, we aimed to determine whether this epigenetic mark is present in DNA of the hepatopancreas of the land snail Cantareus aspersus and is responsive to Cd exposure. Adult snails were reared under laboratory conditions and exposed to graded amounts of dietary cadmium for 14 days. Weight gain was used as a sublethal endpoint, whereas survival as a lethal endpoint. Our results are the first to provide evidence for the presence of 5hmC in DNA of terrestrial mollusks; 5hmC levels are generally low with the measured values falling below 0.03%. This is also the first study to investigate the interplay of Cd with DNA hydroxymethylation levels in a non-human animal study system. Cadmium retention in the hepatopancreas of C. aspersus increased from a dietary Cd dose of 1 milligram per kilogram dry weight (mg/kg d. wt). For the same treatment, we identified the only significant elevation in percentage of samples with detectable 5hmC levels despite the lack of significant mortalities and changes in weight gain among treatment groups. These findings indicate that 5hmC is an epigenetic mark that may be responsive to Cd exposure, thereby opening a new aspect to invertebrate environmental epigenetics

Epigenetic DNA Methylation Mediating Octopus vulgaris Early Development: Effect of Essential Fatty Acids Enriched Diet

The common octopus, Octopus vulgaris, is a good candidate for aquaculture but a sustainable production is still unviable due to an almost total mortality during the paralarvae stage. DNA methylation regulates gene expression in the eukaryotic genome, and has been shown to exhibit plasticity throughout O. vulgaris life cycle, changing profiles from paralarvae to adult stages. This pattern of methylation could be sensitive to small alterations in nutritional and environmental conditions during the species early development, thus impacting on its health, growth and survival. In this sense, a full understanding of the epigenetic mechanisms operating during O. vulgaris development would contribute to optimizing the culture conditions for this species. Paralarvae of O. vulgaris were cultured over 28 days post-hatching (dph) using two different Artemia sp. based diets: control and a long chain polyunsaturated fatty acids (LC-PUFA) enriched diet. The effect of the diets on the paralarvae DNA global methylation was analyzed by Methyl-Sensitive Amplification Polymorphism (MSAP) and global 5-methylcytosine enzyme-linked immunosorbent assay (ELISA) approaches. The analysis of different methylation states over the time revealed a global demethylation phenomena occurring along O. vulgaris early development being directly driven by the age of the paralarvae. A gradual decline in methylated loci (hemimethylated, internal cytosine methylated, and hypermethylated) parallel to a progressive gain in non-methylated (NMT) loci toward the later sampling points was verified regardless of the diet provided and demonstrate a pre-established and well-defined demethylation program during its early development, involving a 20% of the MSAP loci. In addition, a differential behavior between diets was also observed at 20 dph, with a LC-PUFA supplementation effect over the methylation profiles. The present results show significant differences on the paralarvae methylation profiles during its development and a diet effect on these changes. It is characterized by a process of demethylation of the genome at the paralarvae stage and the influence of diet to favor this methylation loss.En prens

Validation of remote collection and quantification of blood Neurofilament light in neurological diseases

Promising blood-based biomarkers of neuropathology have emerged with potential for therapeutic development and disease monitoring. However, these tools will require specialist tertiary services for integration into clinical management. Remote sampling for biomarker assessment could ease the burden of in-person clinical visits for such tests and allow for frequent sampling. Here we evaluated a capillary finger-prick collection for remote quantification of blood neurofilament light (NfL), a common blood-based biomarker evident in various neurological disorders, and other exploratory markers of neuronal injury and neuroinflammation (GFAP, tau). Matched samples from venepuncture and finger-prick were collected and processed into plasma and/or serum to directly compare NfL levels across four different neurological conditions (HD, MS, ALS, PD). Two delayed processing conditions were compared, three- and seven-day delay, simulating ambient shipment. Capillary NfL and GFAP concentrations were equivalent to those in venous blood serum and plasma. Only NfL remained stable after seven-day processing delay. Capillary NfL replicated disease group differences displayed in venous blood. This data supports our finger-prick method for remote collection and quantification of NfL. With the widespread applications for NfL across the spectrum of neurological disorders, this has the potential to transform disease monitoring, prognosis, and therapeutic development within clinical practice and research

Evaluating finger-prick blood collection for remote quantification of neurofilament light in neurological diseases

Promising blood-based biomarkers of neuropathology have emerged with potential for therapeutic development and disease monitoring. However, these tools will require specialist tertiary services for integration into clinical management. Remote sampling for biomarker assessment could reduce burden of in-person clinical visits for such tests as well as increasing the sampling frequency and patient geographical outreach. Here, we evaluated a finger-prick blood collection approach for remote quantification of neurofilament light (NfL), a candidate blood-based biomarker evident in various neurological disorders, and other exploratory markers of neuronal injury and neuroinflammation (GFAP, tau). Matched samples from venepuncture and finger-prick were collected and processed into plasma and/or serum to directly compare analyte levels from a multi-disease discovery cohort (n = 54 healthy controls; n = 57 Huntington's disease (HD); n = 34 multiple sclerosis; n = 7 amyotrophic lateral sclerosis; n = 11 Parkinson's disease), and a HD confirmatory cohort (n = 57 healthy controls; n = 64 HD). Two delayed processing conditions were compared, three- and seven-day delay, simulating ambient shipment. Capillary NfL and GFAP concentrations were equivalent to those in venous serum and plasma in the multi-disease discovery cohort and HD confirmatory cohort. Only NfL remained stable after a seven-day processing delay in both venous and capillary serum samples. Using NfL concentrations from capillary blood, we replicated previously published disease group differences measured in venous blood. This data supports our finger-prick approach for remote collection and quantification of NfL. With the widespread applications for NfL across the spectrum of neurological disorders, this has the potential to transform disease monitoring, prognosis, and therapeutic development within clinical practice and research