44,487 research outputs found
Reactive astrocyte-derived neurotoxins are responsible for the neurodegeneration in a model of Parkinson’s disease
No full textAmyloid beta receptors responsible for neurotoxicity and cellular defects in Alzheimer's disease
No full textAlzheimer's disease (AD) is the most common neurodegenerative disease. Although a major cause of AD is the accumulation of amyloid-beta (A beta) peptide that induces neuronal loss and cognitive impairments, our understanding of its neurotoxic mechanisms is limited. Recent studies have identified putative A beta-binding receptors that mediate A beta neurotoxicity in cells and models of AD. Once A beta interacts with a receptor, a toxic signal is transduced into neurons, resulting in cellular defects including endoplasmic reticulum stress and mitochondrial dysfunction. In addition, A beta can also be internalized into neurons through unidentified A beta receptors and induces malfunction of subcellular organelles, which explains some part of A beta neurotoxicity. Understanding the neurotoxic signaling initiated by A beta-receptor binding and cellular defects provide insight into new therapeutic windows for AD. In the present review, we summarize the findings on A beta-binding receptors and the neurotoxicity of oligomeric A beta.
COMPETITIVENESS THROUGH KNOWLEDGE – ASSESSMENT OF THE EUROPEAN UNION MEMBER STATES BASED ON THE KNOWLEDGE ASSESSMENT METHODOLOGY (KAM) DEVELOPED BY THE WORLD BANK
No full textThe present study attempts to make a diagnosis of the progress of European Union member states in the transition towards the knowledge economy. We used the World Bank KAM Methodology developed in the programme Knowledge for Development and the database available on the web page of the World Bank. KAM Methodology was described and the European progress towards the knowledge economy was assessed according to this methodology, with the focus on the Romanian situation, from a comparative perspective.knowledge economy; competitiveness through knowledge
Kam
No full textA woman dances in the dark to transform her body into light and color. “Kam", meaning "Shaman" in old Turkish, is a long-exposure pixilation / 2D animation film expressing the primal, potent energy of the female body.
This animated film made in response to the repressive discourses about the female body investigates how two different techniques of animation (namely, long exposure photography of real movements and 2D drawings) can be combined to create a fierce and exuberant dance flow.
Kam has screened at numerous international festivals, so far winning two awards (Best Experimental Film at International Women Filmmaker Festival – 2021 and Special Mention at Under the Radar Vienna 2022)
You can view a recording of audience responses from Wildsound Festival here.
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Recent advances in preventing neurodegenerative diseases
No full textThe worldwide health-care burden of neurodegenerative diseases is on the rise—a crisis created through a combination of increased caseload and lack of effective treatments. The limitations of pharmacotherapy in these disorders have led to an urgent shift toward research and clinical trials for the development of novel compounds, interventions, and methods that target shared features across the spectrum of neurodegenerative diseases. Research targets include neuronal cell death, mitochondrial dysfunction, protein aggregation, and neuroinflammation. In the past few years, there has been a growth in understanding of the pathophysiologic mechanisms of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, and Huntington’s disease. This increase in knowledge has led to the discovery of numerous novel neuroprotective therapeutic targets. In this context, we reviewed and summarized recent advancements in neuroprotective strategies in neurodegenerative diseases.
Microglia and astrocyte dysfunction in parkinson's disease
No full textWhile glia are essential for regulating the homeostasis in the normal brain, their dysfunction contributes to neurodegeneration in many brain diseases, including Parkinson's disease (PD). Recent studies have identified that PD-associated genes are expressed in glial cells as well as neurons and have crucial roles in microglia and astrocytes. Here, we discuss the role of microglia and astrocytes dysfunction in relation to PD-linked mutations and their implications in PD pathogenesis. A better understanding of microglia and astrocyte functions in PD may provide insights into neurodegeneration and novel therapeutic approaches for PD.
Amelioration of amyloid -FcRIIb neurotoxicity and tau pathologies by targeting LYN
No full textSRC-family kinases (SFKs) have been implicated in Alzheimer's disease (AD), but their mode of action was scarcely understood. Here, we show that LYN plays an essential role in amyloid (A)-triggered neurotoxicity and tau hyperphosphorylation by phosphorylating Fc receptor IIb2 (FcRIIb2). We found that enzyme activity of LYN was increased in the brain of AD patients and was promoted in neuronal cells exposed to A 1-42 (A(1-42)). Knockdown of LYN expression inhibited A(1-42)-induced neuronal cell death. Of note, LYN interacted with FcRIIb2 upon exposure to A(1-42) and phosphorylated FcRIIb2 at Tyr273 within immunoreceptor tyrosine-based inhibitory motif in neuronal cells. With the use of the structure-based drug design, we isolated KICG2576, an ATP-competitive inhibitor of LYN. Determination of cocrystal structure illustrated that KICG2576 bound to the cleft in the LYN kinase domain and inhibited LYN with a half-maximal inhibitory concentration value of 0.15 M. KICG2576 inhibited A- or FcRIIb2-induced cell death, and this effect was better than pyrazolopyrimidine 1, a widely used inhibitor of SFK. Upon exposure to A, KICG2576 blocked the phosphorylation of FcRIIb2 and translocation of phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2, a binding protein to the phosphorylated FcRIIb2, to the plasma membrane, resulting in the inhibition of tau hyperphosphorylation, the downstream event of A(1-42)-FcRIIb2 binding. Furthermore, intracerebroventricular injection of KICG2576 into mice ameliorated A-induced memory impairment. These results suggest that LYN plays a crucial role in A(1-42)-mediated neurotoxicity and tau pathology, providing a therapeutic potential of LYN in AD.Gwon, Y., Kim, S.-H., Kim, H. T., Kam, T.-I., Park, J., Lim, B., Cha, H., Chang, H.-J., Hong, Y. R., Jung, Y.-K. Amelioration of amyloid -FcRIIb neurotoxicity and tau pathologies by targeting LYN.
The Electoral System, the Party System and Accountability in Parliamentary Government
No full textThese files replicate the analyses in the main text and online appendix of Kam Bertelli, Held, "The Electoral System, the Party System and Accountability in Parliamentary Government."
Kam
No full textBackground
“Kam", meaning "Shaman" in old Turkish, is a film expressing the primal, potent energy of the female body via long exposure pixilation/2D animation techniques. The film investigates how the improvisation of a dancer can be recorded via long exposure technique and translated into animated film language to create a manifesto around the selected theme.
Contribution
The film deconstructs & reconstructs movement using the optics field's light recording principles. To record light, first photographers had to expose their subjects for a long period of time, creating traces of movement on the frame. This effect was often considered as undesirable. The film consciously uses this artifact to condense the motion of the dancer in individual pictures, which also allows a stream-of-consciousness approach while creating a new dance flow, which is later combined with 2D animations. The primitive drawings on top of long exposure photographs take form of interventions to the narrative, creating a new, more pronounced layer of expression enforcing the rebellious, transformative energy of the female body. With this film, the combination of long exposure pixilation & 2D animation has been explored for the first time to capture and translate a dance performance.
Significance
Kam is selected to be screened in three international festivals (Xsection, Animated Dance Festival, and Experimental Dance and Music Festival) in USA and France, It was equally selected for screening in Toronto’s Yonge-Dundas Square (YDS) in annual outdoor movie series called Virtual City Cinema, featuring best of short films from around the world.No Full Tex
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