191 research outputs found
European primary datasets of alien bacteria and viruses
Bacteria and viruses are a natural component of Earth biodiversity and play an essential role in biochemical and geological cycles. They may also pose problems outside their native range, where they can negatively impact on natural resources, wildlife, and human health. To address these challenges and develop sustainable conservation strategies, a thorough understanding of their invasion related- factors is needed: origin, country and year of introduction, and pathways dynamics. Yet, alien bacteria and viruses are underrepresented in invasion ecology studies, which limits our ability to quantify their impacts and address future introductions. This study provides primary datasets of alien bacteria and viruses of plants and animals present in the European environment. The datasets contain expert-revised data on 446 taxa and their invasion related- factors across terrestrial and aquatic environments. Taxa information are complemented with spatial occurrences. The datasets provide a basis for collaborative initiatives to improve the collection of alien bacteria and viruses' data, and a starting point for data-driven conservation practices
Dysregulation of the GPR17 receptor in neuroinflammatory diseases: implications for remyelination in multiple sclerosis
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, in which inflammation and myelin disruption contribute to impaired in electrical conduction.
Oligodendrocyte precursor cells (OPCs) are massively recruited to the site of injury to myelinate damaged axons, but in MS patients remyelination is often ineffective. For this reason, therapeutic strategies aimed at fostering this process could block/delay the development of the disease and the consequent disability.
We have previously shown that the membrane receptor GPR17 timely regulates the early stages of OPC differentiation, but, after reaching its highest levels in immature oligodendrocytes, it has to be down-regulated to allow terminal maturation. Any defect in its expression pattern leads to impairment in oligodendrocyte differentiation.
Interestingly, overexpression of GPR17 was found in rodent models of cerebral trauma, ischemia and in lysolecithin induced focal demyelination. Instead, little is known about GPR17 in a primary demyelinating disease such as MS. On this basis, aim of this work has been to characterize GPR17 alterations in a murine model of MS and in human post-mortem MS lesions.
In spinal cord of mice subjected to experimental autoimmune encephalomyelitis (EAE), we observed a marked and persistent upregulation of GPR17 in the OPCs accumulating at demyelinating lesions. Moreover, fate-mapping experiments with transgenic GPR17iCreERT2-GFP reporter mice showed that this increased pool of proliferating cells is blocked at an intermediate stage of differentiation, and cannot fully complete the myelination process, likely due to unfavourable inflammatory environment.
In a similar way, in post-mortem tissues from SPMS patients, many GPR17-positive activated OPCs accumulated at the border of active lesions. In particular, GPR17 was found mainly expressed by hypertrophic cells HLA (human leukocyte antigen or major histocompatibility complex) -positive at within the lesions, suggesting that GPR17 is involved in the reaction to damage in both OPCs and immune cells directly responding to inflammation.
We conclude that the coordinated presence of GPR17 at the membrane of these cells at the lesion sites could be exploited as potential new target to support endogenous remyelination through advanced pharmacological approaches
Automated Detection of Cortical Lesions in Multiple Sclerosis Patients with 7T MRI
The automated detection of cortical lesions (CLs) in patients with multiple sclerosis (MS) is a challenging task that, despite its clinical relevance, has received very little attention. Accurate detection of the small and scarce lesions requires specialized sequences and high or ultra- high field MRI. For supervised training based on multimodal structural MRI at 7T, two experts generated ground truth segmentation masks of 60 patients with 2014 CLs. We implemented a simplified 3D U-Net with three resolution levels (3D U-Net-). By increasing the complexity of the task (adding brain tissue segmentation), while randomly dropping input channels during training, we improved the performance compared to the baseline. Considering a minimum lesion size of 0.75 μL, we achieved a lesion-wise cortical lesion detection rate of 67% and a false positive rate of 42%. However, 393 (24%) of the lesions reported as false positives were post-hoc confirmed as potential or definite lesions by an expert. This indicates the potential of the proposed method to support experts in the tedious process of CL manual segmentation
Tone and Broadband Noise Separation from Acoustic Data of a Scale-Model Counter-Rotating Open Rotor
Renewed interest in contra-rotating open rotor technology for aircraft propulsion application has prompted the development of advanced diagnostic tools for better design and improved acoustical performance. In particular, the determination of tonal and broadband components of open rotor acoustic spectra is essential for properly assessing the noise control parameters and also for validating the open rotor noise simulation codes. The technique of phase averaging has been employed to separate the tone and broadband components from a single rotor, but this method does not work for the two-shaft contra-rotating open rotor. A new signal processing technique was recently developed to process the contra-rotating open rotor acoustic data. The technique was first tested using acoustic data taken of a hobby aircraft open rotor propeller, and reported previously. The intent of the present work is to verify and validate the applicability of the new technique to a realistic one-fifth scale open rotor model which has 12 forward and 10 aft contra-rotating blades operating at realistic forward flight Mach numbers and tip speeds. The results and discussions of that study are presented in this paper
Cerebrospinal Fluid Dendritic Cells Infiltrate the Brain Parenchyma and Target the Cervical Lymph Nodes under Neuroinflammatory Conditions
BACKGROUND: In many neuroinflammatory diseases, dendritic cells (DCs) accumulate in several compartments of the central nervous system (CNS), including the cerebrospinal fluid (CSF). Myeloid DCs invading the inflamed CNS are thus thought to play a major role in the initiation and perpetuation of CNS-targeted autoimmune responses. We previously reported that, in normal rats, DCs injected intra-CSF migrated outside the CNS and reached the B-cell zone of cervical lymph nodes. However, there is yet no information on the migratory behavior of CSF-circulating DCs under neuroinflammatory conditions. METHODOLOGY/PRINCIPAL FINDINGS: To address this issue, we performed in vivo transfer experiments in rats suffering from experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. EAE or control rats were injected intra-CSF with bone marrow-derived myeloid DCs labeled with the fluorescent marker carboxyfluorescein diacetate succinimidyl ester (CFSE). In parallel experiments, fluorescent microspheres were injected intra-CSF to EAE rats in order to track endogenous antigen-presenting cells (APCs). Animals were then sacrificed on day 1 or 8 post-injection and their brain and peripheral lymph nodes were assessed for the presence of microspheres(+) APCs or CFSE(+) DCs by immunohistology and/or FACS analysis. Data showed that in EAE rats, DCs injected intra-CSF substantially infiltrated several compartments of the inflamed CNS, including the periventricular demyelinating lesions. We also found that in EAE rats, as compared to controls, a larger number of intra-CSF injected DCs reached the cervical lymph nodes. This migratory behavior was accompanied by an accentuation of EAE clinical signs and an increased systemic antibody response against myelin oligodendrocyte glycoprotein, a major immunogenic myelin antigen. CONCLUSIONS/SIGNIFICANCE: Altogether, these results indicate that CSF-circulating DCs are able to both survey the inflamed brain and to reach the cervical lymph nodes. In EAE and maybe multiple sclerosis, CSF-circulating DCs may thus support the immune responses that develop within and outside the inflamed CNS
Cortical injury in multiple sclerosis; the role of the immune system
The easily identifiable, ubiquitous demyelination and neuronal damage that occurs within the cerebral white matter of patients with multiple sclerosis (MS) has been the subject of extensive study. Accordingly, MS has historically been described as a disease of the white matter. Recently, the cerebral cortex (gray matter) of patients with MS has been recognized as an additional and major site of disease pathogenesis. This acknowledgement of cortical tissue damage is due, in part, to more powerful MRI that allows detection of such injury and to focused neuropathology-based investigations. Cortical tissue damage has been associated with inflammation that is less pronounced to that which is associated with damage in the white matter. There is, however, emerging evidence that suggests cortical damage can be closely associated with robust inflammation not only in the parenchyma, but also in the neighboring meninges. This manuscript will highlight the current knowledge of inflammation associated with cortical tissue injury. Historical literature along with contemporary work that focuses on both the absence and presence of inflammation in the cerebral cortex and in the cerebral meninges will be reviewed
Targeted Ablation of Oligodendrocytes Triggers Axonal Damage
Glial dysfunction has been implicated in a number of neurodegenerative diseases. In this study we investigated the consequences of glial and oligodendrocyte ablation on neuronal integrity and survival in Drosophila and adult mice, respectively. Targeted genetic ablation of glia was achieved in the adult Drosophila nervous system using the GAL80-GAL4 system. In mice, oligodendrocytes were depleted by the injection of diphtheria toxin in MOGi-Cre/iDTR double transgenic animals. Acute depletion of oligodendrocytes induced axonal injury, but did not cause neuronal cell death in mice. Ablation of glia in adult flies triggered neuronal apoptosis and resulted in a marked reduction in motor performance and lifespan. Our study shows that the targeted depletion of glia triggers secondary neurotoxicity and underscores the central contribution of glia to neuronal homeostasis. The models used in this study provide valuable systems for the investigation of therapeutic strategies to prevent axonal or neuronal damage
Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: a retrospective autopsy cohort analysis
Epstein-Barr Virus Stimulates Torque Teno Virus Replication: A Possible Relationship to Multiple Sclerosis
Viral infections have been implicated in the pathogenesis of multiple sclerosis. Epstein-Barr virus (EBV) has frequently been investigated as a possible candidate and torque teno virus (TTV) has also been discussed in this context. Nevertheless, mechanistic aspects remain unresolved. We report viral replication, as measured by genome amplification, as well as quantitative PCR of two TTV-HD14 isolates isolated from multiple sclerosis brain in a series of EBV-positive and -negative lymphoblastoid and Burkitt's lymphoma cell lines. Our results demonstrate the replication of both transfected TTV genomes up to day 21 post transfection in all the evaluated cell lines. Quantitative amplification indicates statistically significant enhanced TTV replication in the EBV-positive cell lines, including the EBV-converted BJAB line, in comparison to the EBV-negative Burkitt's lymphoma cell line BJAB. This suggests a helper effect of EBV infections in the replication of TTV. The present study provides information on a possible interaction of EBV and TTV in the etiology and progression of multiple sclerosis
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