Immunomodulatory effects of microbiota-derived metabolites at the crossroad of neurodegenerative diseases and viral infection: network-based bioinformatics insights

Bidirectional cross-talk between commensal microbiota and the immune system is essential for the regulation of immune responses and the formation of immunological memory. Perturbations of microbiome-immune system interactions can lead to dysregulated immune responses against invading pathogens and/or to the loss of self-tolerance, leading to systemic inflammation and genesis of several immune-mediated pathologies, including neurodegeneration. In this paper, we first investigated the contribution of the immunomodulatory effects of microbiota (bacteria and fungi) in shaping immune responses and influencing the formation of immunological memory cells using a network-based bioinformatics approach. In addition, we investigated the possible role of microbiota-host-immune system interactions and of microbiota-virus interactions in a group of neurodegenerative diseases (NDs): Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Parkinson’s disease (PD) and Alzheimer’s disease (AD). Our analysis highlighted various aspects of the innate and adaptive immune response systems that can be modulated by microbiota, including the activation and maturation of microglia which are implicated in the development of NDs. It also led to the identification of specific microbiota components which might be able to influence immune system processes (ISPs) involved in the pathogenesis of NDs. In addition, it indicated that the impact of microbiota-derived metabolites in influencing disease-associated ISPs, is higher in MS disease, than in AD, PD and ALS suggesting a more important role of microbiota mediated-immune effects in MS

Occupying wide open spaces? Late Pleistocene hunter–gatherer activities in the Eastern Levant

With a specific focus on eastern Jordan, the Epipalaeolithic Foragers in Azraq Project explores changing hunter-gatherer strategies, behaviours and adaptations to this vast area throughout the Late Pleistocene. In particular, we examine how lifeways here (may have) differed from surrounding areas and what circumstances drew human and animal populations to the region. Integrating multiple material cultural and environmental datasets, we explore some of the strategies of these eastern Jordanian groups that resulted in changes in settlement, subsistence and interaction and, in some areas, the occupation of substantial aggregation sites. Five years of excavation at the aggregation site of Kharaneh IV suggest some very intriguing technological and social on-site activities, as well as adaptations to a dynamic landscape unlike that of today. Here we discuss particular aspects of the Kharaneh IV material record within the context of ongoing palaeoenvironmental reconstructions and place these findings in the wider spatial and temporal narratives of the Azraq Basin

Flash Flood Susceptibility Evaluation in Human-Affected Areas Using Geomorphological Methods—The Case of 9 August 2020, Euboea, Greece. A GIS-Based Approach.

Flash floods occur almost exclusively in small basins, and they are common in small Mediterranean catchments. They pose one of the most common natural disasters, as well as one of the most devastating. Such was the case of the recent flood in Euboea island, in Greece, in August 2020. A field survey was accomplished after the 2020 flash floods in order to record the main impacts of the event and identify the geomorphological and man-made causes. The flash flood susceptibility in the urbanized alluvial fans was further assessed using a Geographic Information System (GIS)-based approach. Our findings suggest that a large portion of the alluvial fans of Politika, Poros and Mantania streams are mainly characterized by high and very high hazard. In fact, ~27% of the alluvial fans of Politika and Poros streams are characterized with very high susceptibility, and ~54% of Psachna area. GIS results have been confirmed by field observations after the 2020 flash flood, with significant damages noted, such as debris flows and infrastructure damages, in buildings, bridges and the road networks. In addition, even though the adopted approach may be more time-consuming in comparison to purely computational methods, it has the potential of being more accurate as it combines field observations and the effect of past flooding events

Implementation of GIS technologies for planning the valorisation of agricultural waste: the TANGO-Circular Project

The volume of waste produced by agricultural activities is constantly rising, due to the continuous increase of crop and livestock production, aimed to cover the nutritional needs of the accreting population of the Planet. According to recent estimations, the total amount of waste produced in the whole EU by the agricultural sector during the period 2010-2016, has been around 18.4 billion tons, which represents an average of 2.6 billion tons/year. This number is slightly exceeding the amount of waste from all other sectors combined. This enormous mass of waste has a significant environmental impact, which needs suitable solutions to reduce the carbon footprint of agriculture, while increasing the economic income for farmers. A promising way to reduce agricultural waste, passes through the valorization of agricultural co-products, by-products and residues, as well as other non-organic materials - such as plastics, widely used in crop cultivation and animal production - after the end of their working life. In order to involve farmers to play an active role on this issue, contributing to transform what they currently consider as a “waste” into a new “resource”, under the perspective of a circular economy and for a more sustainable agriculture, the Project TANGO-Circular has been financed by the EU Erasmus+ Programme. Aim of this Project is to train farmers and other agricultural stakeholders to be involved in finding viable solutions to exploit unusable remains of crops or animal farms, so as to enhance their financial input, while simultaneously contribute to reducing the environmental impact of their agro-livestock activities. With the aim to plan the valorization of agricultural waste, under the TANGO-Circular Project, a Geographical Information System (GIS) has been implemented through an open-access software (Q-GIS). This GIS has been structured into a first part dedicated to the quantification of agricultural waste flows – both organic, coming from agroindustrial activities, and not-organic, such as plastics - and a second part, focused on the spatial distribution of these flows in the study area of the project partners. Through GIS, the areas with high density of agricultural waste have been pointed out, and the suitable location of potential collection centres has been proposed. The maps that have been produced, as well as the GIS database, are always updatable tools, useful also for monitoring and optimizing the sorting and collection of agricultural waste from the farms, their suitable treatments and transport to the collection centers or recycling stations. The implemented GIS methodology has revealed very useful to support farmers and their associations, as well as all public bodies interested to govern the agricultural waste flows, to individuate possible solutions designed for the valorization of these flows, in the perspective of a circular economy. The sustainability and economic, territorial, environmental and social convenience of each form of valorization designed have been investigated, and criticalities associated with each phase of the process and consequent implementation of appropriate solutions to each problem have been addressed. Finally, further possible solutions, aimed at an increasingly better valorization of these flows, have been proposed as well

Phenotype-dependent apoptosis signalling in mesothelioma cells after selenite exposure

<p>Abstract</p> <p>Background</p> <p>Selenite is a promising anticancer agent which has been shown to induce apoptosis in malignant mesothelioma cells in a phenotype-dependent manner, where cells of the chemoresistant sarcomatoid phenotype are more sensitive.</p> <p>Methods</p> <p>In this paper, we investigate the apoptosis signalling mechanisms in sarcomatoid and epithelioid mesothelioma cells after selenite treatment. Apoptosis was measured with the Annexin-PI assay. The mitochondrial membrane potential, the expression of Bax, Bcl-XL, and the activation of caspase-3 were assayed with flow cytometry and a cytokeratin 18 cleavage assay. Signalling through JNK, p38, p53, and cathepsins B, D, and E was investigated with chemical inhibitors. Furthermore, the expression, nuclear translocation and DNA-binding activity of p53 was investigated using ICC, EMSA and the monitoring of p21 expression as a downstream event. Levels of thioredoxin (Trx) were measured by ELISA.</p> <p>Results</p> <p>In both cell lines, 10 μM selenite caused apoptosis and a marked loss of mitochondrial membrane potential. Bax was up-regulated only in the sarcomatoid cell line, while the epithelioid cell line down-regulated Bcl-XL and showed greater caspase-3 activation. Nuclear translocation of p53 was seen in both cell lines, but very little p21 expression was induced. Chemical inhibition of p53 did not protect the cells from apoptosis. p53 lost its DNA binding ability after selenite treatment and was enriched in an inactive form. Levels of thioredoxin decreased after selenite treatment. Chemical inhibition of MAP kinases and cathepsins showed that p38 and cathepsin B had some mediatory effect while JNK had an anti-apoptotic role.</p> <p>Conclusion</p> <p>We delineate pathways of apoptosis signalling in response to selenite, showing differences between epithelioid and sarcomatoid mesothelioma cells. These differences may partly explain why sarcomatoid cells are more sensitive to selenite.</p

Child studies multiple – collaborative play for thinking through theories and methods

This text is an exploration of collaborative thinking and writing through theories, methods, and experiences on the topic of the child, children, and childhood. It is a collaborative written text (with 32 authors) that sprang out of the experimental workshop Child Studies Multiple. The workshop and this text are about daring to stay with mess, “un-closure” , and uncertainty in order to investigate the (e)motions and complexities of being either a child or a researcher. The theoretical and methodological processes presented here offer an opportunity to shake the ground on which individual researchers stand by raising questions about scientific inspiration, theoretical and methodological productivity, and thinking through focusing on process, play, and collaboration. The effect of this is a questioning of the singular academic ‘I’ by exploring and showing what a plural ‘I’ can look like. It is about what the multiplicity of voice can offer research in a highly individualistic time. The article allows the reader to follow and watch the unconventional trial-and-error path of the ongoing-ness of exploring theories and methods together as a research community via methods of drama, palimpsest, and fictionary

Identification of viral-mediated pathogenic mechanisms in neurodegenerative diseases using network-based approaches

Abstract During the course of a viral infection, virus–host protein–protein interactions (PPIs) play a critical role in allowing viruses to replicate and survive within the host. These interspecies molecular interactions can lead to viral-mediated perturbations of the human interactome causing the generation of various complex diseases. Evidences suggest that viral-mediated perturbations are a possible pathogenic etiology in several neurodegenerative diseases (NDs). These diseases are characterized by chronic progressive degeneration of neurons, and current therapeutic approaches provide only mild symptomatic relief; therefore, there is unmet need for the discovery of novel therapeutic interventions. In this paper, we initially review databases and tools that can be utilized to investigate viral-mediated perturbations in complex NDs using network-based analysis by examining the interaction between the ND-related PPI disease networks and the virus–host PPI network. Afterwards, we present our theoretical-driven integrative network-based bioinformatics approach that accounts for pathogen–genes–disease-related PPIs with the aim to identify viral-mediated pathogenic mechanisms focusing in multiple sclerosis (MS) disease. We identified seven high centrality nodes that can act as disease communicator nodes and exert systemic effects in the MS-enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways network. In addition, we identified 12 KEGG pathways, 5 Reactome pathways and 52 Gene Ontology Immune System Processes by which 80 viral proteins from eight viral species might exert viral-mediated pathogenic mechanisms in MS. Finally, our analysis highlighted the Th17 differentiation pathway, a disease communicator node and part of the 12 underlined KEGG pathways, as a key viral-mediated pathogenic mechanism and a possible therapeutic target for MS disease.</jats:p

Identification of viral-mediated pathogenic mechanisms in neurodegenerative diseases using network-based approaches

AbstractDuring the course of a viral infection, virus-host protein-protein interactions (PPIs) play a critical role in allowing viruses to evade host immune responses, replicate and hence survive within the host. These interspecies molecular interactions can lead to viral-mediated perturbations of the human interactome causing the generation of various complex diseases, from cancer to neurodegenerative diseases (NDs). There are evidences suggesting that viral-mediated perturbations are a possible pathogenic aetiology in several NDs such as Amyloid Later Sclerosis, Parkinson’s disease, Alzheimer’s disease and Multiple Sclerosis (MS), as they can cause degeneration of neurons via both direct and/or indirect actions. These diseases share several common pathological mechanisms, as well as unique disease mechanisms that reflect disease phenotype. NDs are chronic degenerative diseases of the central nervous system and current therapeutic approaches provide only mild symptomatic relief rather than treating the disease at heart, therefore there is unmet need for the discovery of novel therapeutic targets and pharmacotherapies. In this paper we initially review databases and tools that can be utilized to investigate viral-mediated perturbations in complex NDs using network-based analysis by examining the interaction between the ND-related PPI disease networks and the virus-host PPI network. Afterwards we present our integrative network-based bioinformatics approach that accounts for pathogen-genes-disease related PPIs with the aim to identify viral-mediated pathogenic mechanisms focusing in MS disease. We identified 7 high centrality nodes that can act as disease communicator nodes and exert systemic effects in the MS enriched KEGG pathways network. In addition, we identified 12 KEGG pathways targeted by 67 viral proteins from 8 viral species that might exert viral-mediated pathogenic mechanisms in MS by interacting with the disease communicator nodes. Finally, our analysis highlighted the Th17 differentiation pathway, a hub-bottleneck disease communicator node and part of the 12 underlined KEGG pathways, as a key viral-mediated pathogenic mechanism and a possible therapeutic target for MS disease.</jats:p

Systems Bioinformatics Reveals Possible Relationship between COVID-19 and the Development of Neurological Diseases and Neuropsychiatric Disorders

Coronavirus Disease 2019 (COVID-19) is associated with increased incidence of neurological diseases and neuropsychiatric disorders after infection, but how it contributes to their development remains under investigation. Here, we investigate the possible relationship between COVID-19 and the development of ten neurological disorders and three neuropsychiatric disorders by exploring two pathological mechanisms: (i) dysregulation of host biological processes via virus&ndash;host protein&ndash;protein interactions (PPIs), and (ii) autoreactivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epitopes with host &ldquo;self&rdquo; proteins via molecular mimicry. We also identify potential genetic risk factors which in combination with SARS-CoV-2 infection might lead to disease development. Our analysis indicated that neurodegenerative diseases (NDs) have a higher number of disease-associated biological processes that can be modulated by SARS-CoV-2 via virus&ndash;host PPIs than neuropsychiatric disorders. The sequence similarity analysis indicated the presence of several matching 5-mer and/or 6-mer linear motifs between SARS-CoV-2 epitopes with autoreactive epitopes found in Alzheimer&rsquo;s Disease (AD), Parkinson&rsquo;s Disease (PD), Myasthenia Gravis (MG) and Multiple Sclerosis (MS). The results include autoreactive epitopes that recognize amyloid-beta precursor protein (APP), microtubule-associated protein tau (MAPT), acetylcholine receptors, glial fibrillary acidic protein (GFAP), neurofilament light polypeptide (NfL) and major myelin proteins. Altogether, our results suggest that there might be an increased risk for the development of NDs after COVID-19 both via autoreactivity and virus&ndash;host PPIs

DataSheet_1_Immunomodulatory effects of microbiota-derived metabolites at the crossroad of neurodegenerative diseases and viral infection: network-based bioinformatics insights.docx

Bidirectional cross-talk between commensal microbiota and the immune system is essential for the regulation of immune responses and the formation of immunological memory. Perturbations of microbiome-immune system interactions can lead to dysregulated immune responses against invading pathogens and/or to the loss of self-tolerance, leading to systemic inflammation and genesis of several immune-mediated pathologies, including neurodegeneration. In this paper, we first investigated the contribution of the immunomodulatory effects of microbiota (bacteria and fungi) in shaping immune responses and influencing the formation of immunological memory cells using a network-based bioinformatics approach. In addition, we investigated the possible role of microbiota-host-immune system interactions and of microbiota-virus interactions in a group of neurodegenerative diseases (NDs): Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Parkinson’s disease (PD) and Alzheimer’s disease (AD). Our analysis highlighted various aspects of the innate and adaptive immune response systems that can be modulated by microbiota, including the activation and maturation of microglia which are implicated in the development of NDs. It also led to the identification of specific microbiota components which might be able to influence immune system processes (ISPs) involved in the pathogenesis of NDs. In addition, it indicated that the impact of microbiota-derived metabolites in influencing disease-associated ISPs, is higher in MS disease, than in AD, PD and ALS suggesting a more important role of microbiota mediated-immune effects in MS.</p