A single-cell transcriptomic analysis of Neuroblastomas revealed a selective cGAS-STING pathway suppression in malignant cells

Neuroblastoma is a disease of disordered development accounting for 15% of childhood cancer deaths. The "cold"immunophenotype frequently occurring of these tumors is likely to contribute to its aggressiveness and refractoriness to treatments, including immune checkpoint blockade, observed in high risk neuroblastoma. The mechanisms that contribute to the cold immunostate have not been elucidated, yet. However, recent studies have reported the involvement of MYCN amplification in reducing the immune infiltrate in high-risk Neuroblastoma tumors. Its action mainly concerns suppressed interferon responses and pro-inflammatory pathways. An important pathway deputed to the activation of type I interferon responses and pro-inflammatory cytokines release is the cyclic GMP-AMP synthase (cGAS) - stimulator of interferon genes (STING) cytosolic DNA sensing pathway. Recent preclinical studies suggest a promising therapeutic effect of cGAS-STING pathway reactivation in Neuroblastomas. However, very little is known about the regulation of the cGAS-STING pathway in Neuroblastoma malignant cells, and its relationship with the MYCN amplification state. To this end, we performed a single-cell transcriptomic analysis of primary human Neuroblastoma cells compared with their normal fetal and embryonic progenitors. The results of the high-resolution analysis of cGAS-STING pathway showed that Neuroblastomas malignant cells have a much lower expression of this pathway compared to normal progenitors and other cell phenotypes populating the tumor microenvironment, possibly acquiring an evolutionary advantage. Moreover, the cGAS-STING pathway anticorrelated with MYCN expression suggesting a putative regulatory mechanism of the STING pathwa

Is Chronic Exposure to Raw Water a Possible Risk Factor for Amyotrophic Lateral Sclerosis? A Pilot Case-Control Study

Background: The etiopathogenesis of amyotrophic lateral sclerosis (ALS) is still largely unknown. Methods: We performed a case-control study (33 cases and 35 controls) in Umbria, Italy. We investigated associations between common lifestyle, clinical factors, as well as environmental exposures potentially implicated with ALS onset. Face-to-face interviews were carried out. All cases were recruited and diagnosed according to El Escorial criteria. Case-control comparisons were made for educational and residential status, occupational exposures, and clinical and lifestyle factors prior to cases’ dates of diagnosis. Results: Our results showed an increased risk of ALS for subjects chronically exposed to raw water use (odds ratio (OR) = 6.55, 95% confidence interval (CI): 2.24–19.12). Garden activities showed a tight association with ALS as well, very likely as a consequence of chronic raw water exposure. Indeed, we could exclude an impact for pesticides, as no significant differences were observed in pesticide exposure in the two groups interviewed. However, cases were more often exposed to fertilizers. After adjustment for age, sex, and heavy physical activities, exposure to raw water was still associated with increased ALS risk (OR = 4.74, 95% CI: 1.33–16.85). Discussion: These findings suggest an association between ALS and exposure to raw water, which should be further investigated for the presence of chemicals interfering with nervous system functionality

Is Chronic Exposure to Raw Water a Possible Risk Factor for Amyotrophic Lateral Sclerosis? A Pilot Case-Control Study

Background: The etiopathogenesis of amyotrophic lateral sclerosis (ALS) is still largely unknown. Methods: We performed a case-control study (33 cases and 35 controls) in Umbria, Italy. We investigated associations between common lifestyle, clinical factors, as well as environmental exposures potentially implicated with ALS onset. Face-to-face interviews were carried out. All cases were recruited and diagnosed according to El Escorial criteria. Case-control comparisons were made for educational and residential status, occupational exposures, and clinical and lifestyle factors prior to cases’ dates of diagnosis. Results: Our results showed an increased risk of ALS for subjects chronically exposed to raw water use (odds ratio (OR) = 6.55, 95% confidence interval (CI): 2.24–19.12). Garden activities showed a tight association with ALS as well, very likely as a consequence of chronic raw water exposure. Indeed, we could exclude an impact for pesticides, as no significant differences were observed in pesticide exposure in the two groups interviewed. However, cases were more often exposed to fertilizers. After adjustment for age, sex, and heavy physical activities, exposure to raw water was still associated with increased ALS risk (OR = 4.74, 95% CI: 1.33–16.85). Discussion: These findings suggest an association between ALS and exposure to raw water, which should be further investigated for the presence of chemicals interfering with nervous system functionality.</jats:p

VirIoT: A Cloud of Things That Offers IoT Infrastructures as a Service

Many cloud providers offer IoT services that simplify the collection and processing of IoT information. However, the IoT infrastructure composed of sensors and actuators that produces this information remains outside the cloud; therefore, application developers must install, connect and manage the cloud. This requirement can be a market barrier, especially for small/medium software companies that cannot afford the infrastructural costs associated with it and would only prefer to focus on IoT application developments. Motivated by the wish to eliminate this barrier, this paper proposes a Cloud of Things platform, called VirIoT, which fully brings the Infrastructure as a service model typical of cloud computing to the world of Internet of Things. VirIoT provides users with virtual IoT infrastructures (Virtual Silos) composed of virtual things, with which users can interact through dedicated and standardized broker servers in which the technology can be chosen among those offered by the platform, such as oneM2M, NGSI and NGSI-LD. VirIoT allows developers to focus their efforts exclusively on IoT applications without worrying about infrastructure management and allows cloud providers to expand their IoT services portfolio. VirIoT uses external things and cloud/edge computing resources to deliver the IoT virtualization services. Its open-source architecture is microservice-based and runs on top of a distributed Kubernetes platform with nodes in central and edge data centers. The architecture is scalable, efficient and able to support the continuous integration of heterogeneous things and IoT standards, taking care of interoperability issues. Using a VirIoT deployment spanning data centers in Europe and Japan, we conducted a performance evaluation with a two-fold objective: showing the efficiency and scalability of the architecture; and leveraging VirIoT’s ability to integrate different IoT standards in order to make a fair comparison of some open-source IoT Broker implementations, namely Mobius for oneM2M, Orion for NGSIv2, Orion-LD and Scorpio for NGSI-LD.</jats:p

VirIoT: A Cloud of Things That Offers IoT Infrastructures as a Service

Many cloud providers offer IoT services that simplify the collection and processing of IoT information. However, the IoT infrastructure composed of sensors and actuators that produces this information remains outside the cloud; therefore, application developers must install, connect and manage the cloud. This requirement can be a market barrier, especially for small/medium software companies that cannot afford the infrastructural costs associated with it and would only prefer to focus on IoT application developments. Motivated by the wish to eliminate this barrier, this paper proposes a Cloud of Things platform, called VirIoT, which fully brings the Infrastructure as a service model typical of cloud computing to the world of Internet of Things. VirIoT provides users with virtual IoT infrastructures (Virtual Silos) composed of virtual things, with which users can interact through dedicated and standardized broker servers in which the technology can be chosen among those offered by the platform, such as oneM2M, NGSI and NGSI-LD. VirIoT allows developers to focus their efforts exclusively on IoT applications without worrying about infrastructure management and allows cloud providers to expand their IoT services portfolio. VirIoT uses external things and cloud/edge computing resources to deliver the IoT virtualization services. Its open-source architecture is microservice-based and runs on top of a distributed Kubernetes platform with nodes in central and edge data centers. The architecture is scalable, efficient and able to support the continuous integration of heterogeneous things and IoT standards, taking care of interoperability issues. Using a VirIoT deployment spanning data centers in Europe and Japan, we conducted a performance evaluation with a two-fold objective: showing the efficiency and scalability of the architecture; and leveraging VirIoT’s ability to integrate different IoT standards in order to make a fair comparison of some open-source IoT Broker implementations, namely Mobius for oneM2M, Orion for NGSIv2, Orion-LD and Scorpio for NGSI-LD

No Identical "Mesenchymal Stem Cells" at Different Times and Sites: Human Committed Progenitors of Distinct Origin and Differentiation Potential Are Incorporated as Adventitial Cells in Microvessels

A widely shared view reads that mesenchymal stem/stromal cells ("MSCs") are ubiquitous in human connective tissues, can be defined by a common in vitro phenotype, share a skeletogenic potential as assessed by in vitro differentiation assays, and coincide with ubiquitous pericytes. Using stringent in vivo differentiation assays and transcriptome analysis, we show that human cell populations from different anatomical sources, regarded as "MSCs" based on these criteria and assumptions, actually differ widely in their transcriptomic signature and in vivo differentiation potential. In contrast, they share the capacity to guide the assembly of functional microvessels in vivo, regardless of their anatomical source, or in situ identity as perivascular or circulating cells. This analysis reveals that muscle pericytes, which are not spontaneously osteochondrogenic as previously claimed, may indeed coincide with an ectopic perivascular subset of committed myogenic cells similar to satellite cells. Cord blood-derived stromal cells, on the other hand, display the unique capacity to form cartilage in vivo spontaneously, in addition to an assayable osteogenic capacity. These data suggest the need to revise current misconceptions on the origin and function of so-called "MSCs," with important applicative implications. The data also support the view that rather than a uniform class of "MSCs," different mesoderm derivatives include distinct classes of tissue-specific committed progenitors, possibly of different developmental origin.publisher: Elsevier articletitle: No Identical “Mesenchymal Stem Cells” at Different Times and Sites: Human Committed Progenitors of Distinct Origin and Differentiation Potential Are Incorporated as Adventitial Cells in Microvessels journaltitle: Stem Cell Reports articlelink: http://dx.doi.org/10.1016/j.stemcr.2016.05.011 content_type: article copyright: © 2016 The Authors.status: publishe

No Identical “Mesenchymal Stem Cells” at Different Times and Sites: Human Committed Progenitors of Distinct Origin and Differentiation Potential Are Incorporated as Adventitial Cells in Microvessels

SummaryA widely shared view reads that mesenchymal stem/stromal cells (“MSCs”) are ubiquitous in human connective tissues, can be defined by a common in vitro phenotype, share a skeletogenic potential as assessed by in vitro differentiation assays, and coincide with ubiquitous pericytes. Using stringent in vivo differentiation assays and transcriptome analysis, we show that human cell populations from different anatomical sources, regarded as “MSCs” based on these criteria and assumptions, actually differ widely in their transcriptomic signature and in vivo differentiation potential. In contrast, they share the capacity to guide the assembly of functional microvessels in vivo, regardless of their anatomical source, or in situ identity as perivascular or circulating cells. This analysis reveals that muscle pericytes, which are not spontaneously osteochondrogenic as previously claimed, may indeed coincide with an ectopic perivascular subset of committed myogenic cells similar to satellite cells. Cord blood-derived stromal cells, on the other hand, display the unique capacity to form cartilage in vivo spontaneously, in addition to an assayable osteogenic capacity. These data suggest the need to revise current misconceptions on the origin and function of so-called “MSCs,” with important applicative implications. The data also support the view that rather than a uniform class of “MSCs,” different mesoderm derivatives include distinct classes of tissue-specific committed progenitors, possibly of different developmental origin

Pesticides and their metabolites in selected Italian groundwater and surface water used for drinking

The control of groundwater and surface water quality in relation to the presence of pesticides and their metabolites is a rather complicated task. National and local authorities with the responsibility to guarantee an adequate quality of water cannot rely on international guidelines for monitoring activities. In a national project, forty-three pesticides and pesticide metabolites were selected on the basis of sale, monitoring and physical-chemical data, and investigated from some of the main Italian agricultural areas, susceptible to pesticide contamination. Twelve compounds were found in the tested water samples at levels exceeding the 0.1 µg/L European Union (EU) limit for drinking water (European Directive 98/83/EC). Maximum levels up to 0.62 were determined. Several water samples were characterized by the simultaneous occurrence of pesticides and their metabolites (up to ten). In some samples, the total concentration of pesticides and their metabolites was higher than the EU limit of 0.5 µg/L. Total triazine concentrations up to 1.02 µg/L were found. In all the cases the highest concentrations were well below the respective guideline values defined by the World Health Organization (WHO) for drinking water quality