Iron Homeostasis in Neuron-Glia Interaction

One major function of glial cells is to support neurons and create an environment that allows fast signal propagation. However, when neurons are ensheathed, they also get isolated from the extracellular environment and can no longer take up factors required for growth and function. Hence, glial cells have to regulate the neurons’ metabolic and trophic support. To identify candidate genes that are necessary for this support, we initiated a RNA interference screen in Drosophila peripheral nerves. In a screen for highly conserved molecules, we could successfully detect genes that are both required in glial cells and important for neuronal architecture and function. We found that pan-glial inhibition of p24-1 resulted in axonal loss, changed nerve architecture, transportation failure of axonal vesicles, migration defects of photoreceptor cells and swellings of neuronal mitochondria. p24 proteins act in the secretory pathway to shuttle cargo molecules through the biosynthetic pathway. A second p24 family member, opossum, reproduced the p24-1 phenotype revealing that they act in concert. Thus, we tried to identify the p24-1 cargo in a secondary RNAi screen. The iron binding protein Ferritin1 heavy chain was identified which displayed the same peripheral nerve phenotype as p24-1 knockdown. By in vivo and in vitro studies, we could show that Fer1HCH is released from glia cells and taken up by neurons. The inhibition of glial iron release caused accumulations of toxic ferrous iron resulting in ferroptosis. The application of inhibitors, which chelate iron or inhibit ferroptosis, reduced glial and axonal phenotypes. However, the transport defect of axonal vesicles was not recovered. As iron is essential for mitochondrial function, we assumed that iron import is required in neurons for energy production. Thus, we aimed to measure the effect of iron deprivation on neurons. Therefore, two binary expression systems were combined allowing for manipulations on glial cells and contemporaneous isolation of translating ribosomes from neurons. We found that several iron responsive transcripts are down-regulated upon blockage of glial Fer1HCH secretion. Hence, we identified a route for iron import into the nervous system of Drosophila and could show that blockage of this transport caused glial ferroptosis

Life in school : - A teacher student´s hope for a non-suicidal Sweden

Självmord är ett folkhälsoproblem, årligen tar ca 1500 livet av sig i Sverige och 1/3 av dessa är under 24 år. Vad krävs egentligen för att rädda ett av dessa liv? Ambivalensen hos självmordsbenägna människor är sedan tidigare ett känt faktum, men jag frågar mig själv som blivande lärare vad skolan kan göra för att minska antalet självmord/självmordsförsök? Lärare är och förblir den minst utnyttjade tillgången, när det gäller att förhindra självmord. De är så värdefulla, därför att de tillbringar flera timmar med barnet dag in och dag ut än vad de flesta föräldrar gör. De vet också mer om elevens vardagsliv. I mitt examensarbete så har jag arbetat mig fram till relativt enkla saker som skulle kunna förhindra psykisk ohälsa både hos eleverna och hos lärare. Jag har fört samman tre olika sorters litteratur och genom detta fått fram konkreta och enkla arbetsområden som har fått rubrikerna: · Privatliv är skolliv · Våld, hot och mobbning · Mat · Alkohol · Läxor och prov Tankemässigt så befinner jag mig mellan dröm och verklighet och mitt arbete återspeglar verkligen detta. Visionen om en skola som både lärare och elever trivs i ligger som mål.Suicide is a common health problem; 1500 people commit suicide yearly and 1/3 of those are young people under the age of 24. What does it take to save these lives? Suicidal peoples’ ambivalence is already a well-known fact. However, I ask my self as a teacher to be what the school can do to lower these suicide numbers? Teachers are and will remain the least used asset when it comes to prevent suicide. Teachers are important because they spend several hours every day with the children; in some cases more time than parents. Teachers also know more about students’ life outside school. I have in my examination paper discovered some relatively simple things that could prevent psychic unrest in both students and teachers. I have used three different kinds of literature and found some concrete and simple areas of work and given them the headlines: - Private life is school life. - Violence, threats and bulling - Food - Alcohol - Homework and tests In my mind I am between dream and reality and my paper reflex that. The vision about a school both teachers and students are comfortable with is the goal

Viral marknadsföring och den virusliknande spridningen av reklamklipp : En kvantitativ och kvalitativ studie om konsumenters beslutsfattande vid spridning av reklamklipp

Society has become more and more digitalized. Thru time, consumers have built up a resistance for classic marketing strategies such as advertisement in magazines. The resistance for advertisement hasn’t yet become as strong in the digital world. One of many reasons for that is because the digital world is constantly evolving and changing. This change has forced companies to come up with new solutions in order to differentiate them from the competitors. One strategy that has become popular is viral marketing. Viral marketing comes from digital WOM which means that people talk about the company to friends and family. From a consumers’ perspective, viral marketing is still quite new and that is why the authors have chosen to study consumer behaviour regarding sharing advertising videos. In this study, the authors have chosen to collect the primary data with two different methods, a focus group and a survey research. The purpose for the two different methods is to get an overview of the current behaviour but also to get a deeper knowledge of the individuals’ thoughts and the group dynamics that exist. Results of the study shows that consumer behaviour regarding sharing advertising videos depends on; if the video has a capturing story, if the consumer gets affected or if the individual or someone can get benefits from the video. Who is sharing the video, if the video is talked-about or if the individual has been recommended to watch the video are factors that affect if the consumer wants to watch it and where it allows themselves to be exposed to it

Möjligt uppdrag ? : Lärares syn pa det specialpedagogiska uppdraget och lärares specialpedagogiska perspektiv

Denna studie är en kvantitativ studie som baseras på en webbenkat där respondenterna utgör verksamma lärare i grundskolan. Syftet med studien är att öka kunskapen om lärares syn på specialpedagogens arbetsuppgifter och det specialpedagogiska uppdraget. Detta för att öka kunskapen om vad lärarna önskar från specialpedagogens yrkesroll i arbetet med extra anpassningar och särskilt stöd för att kunna stödja alla elevers utveckling och lärande för att precisera syftet är följande frågeställningar centrala:Vilken syn har lärare på det specialpedagogiska uppdraget och vilket specialpedagogiskt perspektiv har lärarna?Utgångspunkten till denna studie är otydligheterna kring specialpedagogens uppdrag och bakomliggande faktorer som påverkar arbetet med elevers utveckling och lärande. Genom att lyfta lärarnas röst kring specialpedagogens arbetsuppgifter söka kunskap om våra två olika professioner utgår från samma eller olika perspektiv. Det kan ha stor betydelse för professionsutovning utifrån att möta verksamheten och dess elever som är i behov av särskilt stöd och för att samverka kring detta med lärama då det är en stor del i det specialpedagogiska uppdraget.Slutsats av studien är att lärarna önskar att specialpedagogen ska arbeta utifrån ett relationellt perspektiv som även är det perspektiv specialpedagoger utbildas för. Lärarnas vilja att specialpedagogen i hög utsträckning ska arbeta med arbetsuppgifter som har fokus på individniva gör att vi kan dra slutsatsen att det fortsatt är det kategoriska perspektivet som är rådande i synen på arbetet med elever i behov av särskilt stöd.Sammanfattningsvis så landar vi i att lärare och specialpedagoger vill åt samma håll, vilket gör det specialpedagogiska uppdraget möjligt, men att dilemmaperspektivet genom skolans frirum och rådande skolkod gör av det ibland kan upplevas som ett omöjligt uppdrag

Hippocampal damage and memory impairment in congenital cyanotic heart disease

Neonatal hypoxia can lead to hippocampal atrophy, which can lead, in turn, to memory impairment. To test the generalizability of this causal sequence, we examined a cohort of 41 children aged 8-16, who, having received the arterial switch operation to correct for transposition of the great arteries, had sustained significant neonatal cyanosis but were otherwise neurodevelopmentally normal. As predicted, the cohort had significant bilateral reduction of hippocampal volumes relative to the volumes of 64 normal controls. They also had significant, yet selective, impairment of episodic memory as measured by standard tests of memory, despite relatively normal levels of intelligence, academic attainment, and verbal fluency. Across the cohort, degree of memory impairment was correlated with degree of hippocampal atrophy suggesting that even as early as neonatal life no other structure can fully compensate for hippocampal injury and its special role in serving episodic long term memory

Neonatal hypoxia, hippocampal atrophy, and memory impairment: evidence of a causal sequence

Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohort's HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life