323,016 research outputs found
Induced Pluripotent Stem Cell (iPSC)-derived Microglia and Organoids for neuronal disease modeling
No full textMicroglia are the principal resident immune cells of the central nervous system (CNS) representing 5-12% of the total cell population in the brain. They are of myeloid origin and their survival and maintenance depend on several cytokines. Microglia play a role in development of the CNS and are constantly engaged in detecting changes in their environment, maintaining homeostasis and protecting against endogenous or environmental injurious agents. Microglia has emerged as an interesting target in many neurodegenerative diseases which deserve to be studied in more detail. Indeed, the mechanisms by which aberrant microglia activation causes neurodegeneration remains unclear. In its activated state, microglia play a role in neurodegeneration of most CNS disorders such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease and Parkinson’s disease. Microglia is implicated in the initiation and in the progress of these diseases, switching from a neuroprotective activated state to a neurotoxic one. Phagocytosis, which involves engulfment and elimination of large cellular structures, is carried out by microglia and can be regulated by an autophagic process which impairment is associated with many neurodegenerative disorders, in part related to an increased release of inducers of the inflammatory response. We preliminary optimized a protocol to differentiate microglia from iPSCs generated from both healthy donor and patients affected by neurodegenerative diseases such as ALS and FTD. Microglia cells were characterized for the expression of specific markers (CD11b, Vimentin, TREM2, TMEM119, IBA1) by immunofluorescence, while their functionality was evaluated by assessing fluorescent latex-beads internalization which confirmed their phagocytic activity. We also evaluated the presence of lipid droplets, consisting in organelles that contain neutral lipids, increasingly being accepted as structural markers of inflammation. In addition, both neural and spinal cord organoids were obtained from iPSCs. Given the important modulatory role in neural death in neurodegenerative diseases, we will establish co-cultures of microglia and iPSC derived organoids combining microglia obtained from patients with organoids derived from controls and vice-versa in order to analyze engraftment of microglia on organoids and to study the interactions between microglial and neural cells
Diffusive author(s), cohesive author: Analysis of S/N (1994)
No full textThis study indicates the ways in which various aspects of the author(s) are brought forth in Dumb type’s performance art, the S/N production. Previous research has suggested a non-hierarchical organization of Dumb type and the absence of a “privileged author” in Dumb type’s collaborative work, S/N. However, the results that I have investigated from member’s interviews on the creative process of S/N along with my analysis of the recorded images of S/N, indicate a different aspect of the author(s). First, S/N was created through, so to speak, the collective ideas of the members of Dumb type. Further, S/N has at least nine quotations from previous performances, installations, and printed writings, besides the work-in-progress technique. Explicating one of the “author functions” as given by Michel Foucault, each text has plural subjects of the author. However, it has been revealed from members’ interviews that Teiji Furuhashi had a decision-making role in selecting the members’ ideas within the performance. Since then, S/N has had plural subjects of creation; however, Furuhashi is one of the subjects of creation along with the “privileged author.” S/N has plural authors (diffusive authors) yet at the same time, it has a “privileged author,” Teiji Furuhashi (cohesive author)
Induced Pluripotent Stem Cell (iPSC)-derived Microglia for ALS modeling
No full textAmyotrophic Lateral Sclerosis (ALS) is a progressive and fatal disease, primarily characterized by the degeneration of upper/lower motoneurons. ALS has a still incompletely understood etiopathology, but it is thought to be caused by the combination of neuronal cell-autonomous and non-cell autonomous mechanisms involving microglia. Microglia, the innate immune cells of the central nervous system, regulate neuroinflammation and their uncontrolled activation, consisting in the aberrant persistence of a pro-inflammatory state, can promote neurotoxicity in ALS.
Aim of our work is to investigate the possible effects of ALS patient-derived microglia in promoting neurotoxicity and the potential neuroprotective role of healthy donor-derived microglia by co-culturing microglial cells obtained from induced pluripotent stem cells (iPSC-microglia) with iPSC-derived motoneurons (iPSC-MNs) and iPSC-derived spinal cord organoids (iPSC-spORGs).
Our work first focused on the preliminary optimization of the differentiation protocols to obtain all the iPSC-derived models to be further used in co-culture conditions. In particular, iPSC-microglia were obtained from healthy donor iPSCs after 55 days of differentiation. Microglia cells were characterized for the expression of specific markers (CD11b, Vimentin, TREM2, TMEM119, IBA1) by immunofluorescence, while their functionality was evaluated by assessing fluorescent latex-beads internalization which confirmed their phagocytic activity. iPSC-MNs were differentiated from embryoid bodies for 34 days and iPSC-spORGs were obtained in 21 days. Both iPSC-MNs and iPSC-spORGs tested positive for the expression of neuronal and motoneuronal markers (SMI-312, Choline Acetyltransferase and HB9) by immunofluorescence and RT-PCR.
Our data indicate that we can efficiently obtain all the iPSC-derived in vitro models to be now used in co-culture systems also from ALS patients’ cells. This will allow to study the possible neurotoxicity of human ALS iPSC-microglia in triggering neuronal death in iPSC-MNs/spORGs and the neuroprotective role of healthy microglia in counteracting neurodegeneration, further contributing to elucidate the interplay of cell-autonomous and non-cell autonomous mechanisms in ALS pathogenesis
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Induced Pluripotent Stem Cell (iPSC)-derived Microglia for ALS modeling
No full textAmyotrophic Lateral Sclerosis (ALS) is a progressive and fatal disease, primarily characterized by the degeneration of upper/lower motoneurons. ALS has a still incompletely understood etiopathology, but it is thought to be caused by the combination of neuronal cell-autonomous and non-cell autonomous mechanisms involving microglia. Microglia, the innate immune cells of the central nervous system, regulate neuroinflammation and their uncontrolled activation, consisting in the aberrant persistence of a pro-inflammatory state, can promote neurotoxicity in ALS.
Aim of our work is to investigate the possible effects of ALS patient-derived microglia in promoting neurotoxicity and the potential neuroprotective role of healthy donor-derived microglia by co-culturing microglial cells obtained from induced pluripotent stem cells (iPSC-microglia) with iPSC-derived motoneurons (iPSC-MNs) and iPSC-derived spinal cord organoids (iPSC-spORGs).
Our work first focused on the preliminary optimization of the differentiation protocols to obtain all the iPSC-derived models to be further used in co-culture conditions. In particular, iPSC-microglia were obtained from healthy donor iPSCs after 55 days of differentiation. Microglia cells were characterized for the expression of specific markers (CD11b, Vimentin, TREM2, TMEM119, IBA1) by immunofluorescence, while their functionality was evaluated by assessing fluorescent latex-beads internalization which confirmed their phagocytic activity. iPSC-MNs were differentiated from embryoid bodies for 34 days and iPSC-spORGs were obtained in 21 days. Both iPSC-MNs and iPSC-spORGs tested positive for the expression of neuronal and motoneuronal markers (SMI-312, Choline Acetyltransferase and HB9) by immunofluorescence and RT-PCR.
Our data indicate that we can efficiently obtain all the iPSC-derived in vitro models to be now used in co-culture systems also from ALS patients’ cells. This will allow to study the possible neurotoxicity of human ALS iPSC-microglia in triggering neuronal death in iPSC-MNs/spORGs and the neuroprotective role of healthy microglia in counteracting neurodegeneration, further contributing to elucidate the interplay of cell-autonomous and non-cell autonomous mechanisms in ALS pathogenesis
Induced Pluripotent Stem Cell (iPSC)-derived Microglia for ALS modeling
No full textAmyotrophic Lateral Sclerosis (ALS) is a progressive and fatal disease, primarily characterized by the degeneration of upper/lower motoneurons. ALS has a still incompletely understood etiopathology, but it is thought to be caused by the combination of neuronal cell-autonomous and non-cell autonomous mechanisms involving microglia. Microglia, the innate immune cells of the central nervous system, regulate neuroinflammation and their uncontrolled activation, consisting in the aberrant persistence of a pro-inflammatory state, can promote neurotoxicity in ALS.
Aim of our work is to investigate the possible effects of ALS patient-derived microglia in promoting neurotoxicity and the potential neuroprotective role of healthy donor-derived microglia by co-culturing microglial cells obtained from induced pluripotent stem cells (iPSC-microglia) with iPSC-derived motoneurons (iPSC-MNs) and iPSC-derived spinal cord organoids (iPSC-spORGs).
Our work first focused on the preliminary optimization of the differentiation protocols to obtain all the iPSC-derived models to be further used in co-culture conditions. In particular, iPSC-microglia were obtained from healthy donor iPSCs after 55 days of differentiation. Microglia cells were characterized for the expression of specific markers (CD11b, Vimentin, TREM2, TMEM119, IBA1) by immunofluorescence, while their functionality was evaluated by assessing fluorescent latex-beads internalization which confirmed their phagocytic activity. iPSC-MNs were differentiated from embryoid bodies for 34 days and iPSC-spORGs were obtained in 21 days. Both iPSC-MNs and iPSC-spORGs tested positive for the expression of neuronal and motoneuronal markers (SMI-312, Choline Acetyltransferase and HB9) by immunofluorescence and RT-PCR.
Our data indicate that we can efficiently obtain all the iPSC-derived in vitro models to be now used in co-culture systems also from ALS patients’ cells. This will allow to study the possible neurotoxicity of human ALS iPSC-microglia in triggering neuronal death in iPSC-MNs/spORGs and the neuroprotective role of healthy microglia in counteracting neurodegeneration, further contributing to elucidate the interplay of cell-autonomous and non-cell autonomous mechanisms in ALS pathogenesis
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Brisk walking improves fitness and metabolic markers in combination antiretroviral therapy (cART)-treated persons
No full textThe potential impact of splenectomy in treatment of visceral Leishmaniasis in a multi-experienced HIV-coinfected patient
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