An Educational Reconstruction of Special Relativity Theory for Secondary Education.

Einstein’s derivation of special relativity theory (SRT), based on hypothetical reasoning and thought experiments, is regarded as a prime example of physics theory development. In secondary education, the introduction of SRT could provide a great opportunity for students to engage in physics theorizing, but this opportunity is largely being missed in current teaching practice. One reason could be that secondary students lack some knowledge of electromagnetism that was central to Einstein’s argument. Therefore, we conducted an educational reconstruction to develop a teaching approach that would not rely on advanced understanding of electromagnetism, yet retain the modes of reasoning that were characteristic of Einstein’s approach. In our reconstruction, we identified the light postulate, which is notoriously difficult for students to grasp, as a central concept. We developed a teaching and learning sequence in which students perform relativistic thought experiments and try different interpretations of the light postulate. Through these activities, students experienced how the new concepts meet the requirements for a good theory. Experimental evaluation of the teaching and learning sequence indicates that this can be a fruitful approach to introduce SRT to secondary students

Molecular misreading: The occurrence of frameshift proteins in different diseases

Neuronal homoeostasis requires a constant balance between biosynthetic and catabolic processes. Eukaryotic cells primarily use two distinct mechanisms for degradation: the proteasome and autophagy of aggregates by the lysosomes. We focused on the UPS (ubiquitin-proteasome system). As a result of molecular misreading, misframed UBB (ubiquitin B) (UBB+1) is generated. UBB+1 accumulates in the neuritic plaques and neurofibrillary tangles in all patients with AD (Alzheimer's disease) and in the neuronal and glial hallmarks of other tauopathies and in polyglutamine diseases such as Huntington's disease. UBB+1 is not present in synucleinopathies such as Parkinson's disease. We showed that UBB+1 causes UPS dysfunction, aggregation and apoptotic cell death. UBB+1 is also present in non-neurological cells, hepatocytes of the diseased liver and in muscles during inclusion body myositis. Other frequently occurring (age-related) diseases such as Type 2 (non-insulin-dependent) diabetes mellitus are currently under investigation. These findings point to the importance of the UPS in diseases and open new avenues for target identification of the main players of the UPS. Treatment of these diseases with tools (e.g. viral RNA interference constructs) to intervene with specific targets is the next step

MLC1 is associated with the Dystrophin-Glycoprotein Complex at astrocytic endfeet

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a progressive cerebral white matter disease with onset in childhood, caused by mutations in the MLC1 gene. MLC1 is a protein with unknown function that is mainly expressed in the brain in astrocytic endfeet at the blood–brain and cerebrospinal fluid–brain barriers. It shares its localization at astrocytic endfeet with the dystrophin-associated glycoprotein complex (DGC). The objective of the present study was to investigate the possible association of MLC1 with the DGC. To test this hypothesis, (co)-localization of DGC-proteins and MLC1 was analyzed by immunohistochemical stainings in gliotic brain tissue from a patient with multiple sclerosis, in glioblastoma tissue and in brain tissue from an MLC patient. In control tissue, a direct protein interaction was tested by immunoprecipitation. Results revealed that MLC1 is co-localized with DGC-proteins in gliotic brain tissue. We demonstrated that both MLC1 and aquaporin-4, a member of the DGC, were redistributed in glioblastoma cells. In MLC brain tissue, we showed absence of MLC1 and altered expression of several DGC-proteins. We demonstrated a direct protein interaction between MLC1 and Kir4.1. From these results we conclude that MLC1 is associated with the DGC at astrocytic endfeet

Marina Abramović : from the artist to the present

Marina Abramovic: From the Artist to the Present mostra una investigació entom a l'artista serbia entre 2010 i 2014. El punt d'inici és The Artist is Present, la seva retrospectiva i obra homónima realitzada al Museum of Modern Art de Nova York, el punt de màxima consolidació d'una artista de performance a la historia de l'art i el reconeixement del públic i la crítica. El treball intenta mostrar la seva trajectoria posterior a l'obra per cobrir el buit bibliografic existent.Marina Abramovic: From the Artist to the Present muestra una investigación realizada entorno a la artista serbia entre 2010 y 2014. El punto de inicio es The Artist is Present, su retrospectiva y obra homónima en el Museum of Modern Art de Nueva York; el punto de máxima consolidación de una artista de performance en la historia del arte y el reconocimiento de público y crítica. El trabajo intenta mostrar la trayectoria posterior a esta obra para cubrir el vacío bibliográfico existente.Marina Abramovic: From the Artist to the Present is a research focused on the serbian artist between 2010 and 2014. The starting point is The Artist is Present, a retrospective in the Museum ofModem Art in New York and the main artwork of the exhibition. It was moment when a performance artist became most stablished by a big institution and art criticism. The main theme of the research is to create a documental resource to group all the artworks from 2010 in a single study

Staging of Neurofibrillary Pathology in Alzheimer's Disease: A Study of the BrainNet Europe Consortium

It has been recognized that molecular classifications will form the basis for neuropathological diagnostic work in the future. Consequently, in order to reach a diagnosis of Alzheimer's disease (AD), the presence of hyperphosphorylated tau (HP-tau) and β-amyloid protein in brain tissue must be unequivocal. In addition, the stepwise progression of pathology needs to be assessed. This paper deals exclusively with the regional assessment of AD-related HP-tau pathology. The objective was to provide straightforward instructions to aid in the assessment of AD-related immunohistochemically (IHC) detected HP-tau pathology and to test the concordance of assessments made by 25 independent evaluators. The assessment of progression in 7-µm-thick sections was based on assessment of IHC labeled HP-tau immunoreactive neuropil threads (NTs). Our results indicate that good agreement can be reached when the lesions are substantial, i.e., the lesions have reached isocortical structures (stage V–VI absolute agreement 91%), whereas when only mild subtle lesions were present the agreement was poorer (I–II absolute agreement 50%). Thus, in a research setting when the extent of lesions is mild, it is strongly recommended that the assessment of lesions should be carried out by at least two independent observers

Comprehensive mRNA Expression Profiling Distinguishes Tauopathies and Identifies Shared Molecular Pathways

Background: Understanding the aetiologies of neurodegenerative diseases such as Alzheimer's disease (AD), Pick's disease (PiD), Progressive Supranuclear Palsy (PSP) and Frontotemporal dementia (FTD) is often hampered by the considerable clinical and molecular overlap between these diseases and normal ageing. The development of high throughput genomic technologies such as microarrays provide a new molecular tool to gain insight in the complexity and relationships between diseases, as they provide data on the simultaneous activity of multiple genes, gene networks and cellular pathways. Methodology/Principal Findings: We have constructed genome wide expression profiles from snap frozen post-mortem tissue from the medial temporal lobe of patients with four neurodegenerative disorders (5 AD, 5 PSP, 5 PiD and 5 FTD patients) and 5 control subjects. All patients were matched for age, gender, ApoE-e and MAPT (tau) haplotype. From all groups a total of 790 probes were shown to be differently expressed when compared to control individuals. The results from these experiments were then used to investigate the correlations between clinical, pathological and molecular findings. From the 790 identified probes we extracted a gene set of 166 probes whose expression could discriminate between these disorders and normal ageing. Conclusions/Significance: From genome wide expression profiles we extracted a gene set of 166 probes whose expression could discriminate between neurological disorders and normal ageing. This gene set can be further developed into an accurate microarray-based classification test. Furthermore, from this dataset we extracted a disease specific set of genes and identified two aging related transcription factors (FOXO1A and FOXO3A) as possible drug targets related to neurodegenerative disease

Intraneuronal Aβ immunoreactivity is not a predictor of brain amyloidosis-β or neurofibrillary degeneration

Amyloid β (Aβ) immunoreactivity in neurons was examined in brains of 32 control subjects, 31 people with Down syndrome, and 36 patients with sporadic Alzheimer’s disease to determine if intraneuronal Aβ immunoreactivity is an early manifestation of Alzheimer-type pathology leading to fibrillar plaque formation and/or neurofibrillary degeneration. The appearance of Aβ immunoreactivity in neurons in infants and stable neuron-type specific Aβ immunoreactivity in a majority of brain structures during late childhood, adulthood, and normal aging does not support this hypothesis. The absence or detection of only traces of reaction with antibodies against 4–13 aa and 8–17 aa of Aβ in neurons indicated that intraneuronal Aβ was mainly a product of α- and γ-secretases (Aβ(17–40/42)). The presence of N-terminally truncated Aβ(17–40) and Aβ(17–42) in the control brains was confirmed by Western blotting and the identity of Aβ(17–40) was confirmed by mass spectrometry. The prevalence of products of α- and γ -secretases in neurons and β- and γ-secretases in plaques argues against major contribution of Aβ-immunopositive material detected in neuronal soma to amyloid deposit in plaques. The strongest intraneuronal Aβ(17–42) immunoreactivity was observed in structures with low susceptibility to fibrillar Aβ deposition, neurofibrillary degeneration, and neuronal loss compared to areas more vulnerable to Alzheimer-type pathology. These observations indicate that the intraneuronal Aβ immunoreactivity detected in this study is not a predictor of brain amyloidosis or neurofibrillary degeneration. The constant level of Aβ immunoreactivity in structures free from neuronal pathology during essentially the entire life span suggests that intraneuronal amino-terminally truncated Aβ represents a product of normal neuronal metabolism

Changes in metabolic activity and estrogen receptors in the human medial mamillary nucleus: relation to sex, aging and Alzheimer's disease

The medial mamillary nucleus (MMN) is situated caudally in the human hypothalamus and is involved in memory processes. In search for putative sites of action in estrogen replacement therapy on memory both in aging and Alzheimer's disease (AD), we aimed at determining whether changes would occur in estrogen receptors (ER) or metabolic activity in the MMN neurons under these conditions in a sex-dependent way. The Golgi apparatus (GA) and cell size, that were previously shown to be good measures of changes in neuronal metabolic activity. were measured in the MMN of 10 young (20-50 years old), 11 elderly (56-76 years old) control men and women and 11 AD patients (54-78 years old). In addition, we investigated whether estrogen receptor alpha or beta (ERalpha or ERbeta) immunoreactivity was altered in the MMN in aging or AD. There were no sex- or AD-related differences in the GA or cell size in the MMN. Both the GA and cell size of the MMN neurons were found to be increased in postmenopausal compared to young control women accompanied by a decrease in the amount of nuclear ERbeta. The percentage of nuclear ERalpha-positive MMN neurons was markedly enhanced in AD patients compared to controls and most prominently in AD men. In AD patients the proportion of nuclear ERalpha-positive neurons was positively correlated to the Braak stages that indicate the progression of the disease. No differences in the proportion of ERbeta-positive neurons were observed between AD and control patients. We propose that estrogens play an inhibitory role with respect to the metabolic activity of human MMN, which is mediated via ERbeta. This inhibitory effect is diminished in postmenopausal women. The role of the enhanced nuclear ERalpha staining in AD. that was also found in other brain areas, remains to be elucidated. (C) 2003 Elsevier Science Inc. All rights reserve

Event diagrams: Supporting student reasoning in special relativity through thought experiments

This chapter presents event diagrams as a representational tool that allows students to visualize relativistic phenomena. It puts particular emphasis on thought experiments that can help students obtain a deeper understanding of physical phenomena that are hard to imagine. The chapter is intended for readers who look for instructional models to teach concepts of special relativity at the secondary school level, and also, for those who wish to learn more about thought experiments as instructional tools. Students perform the thought experiment by drawing light propagation in the event diagram. Compared to the traditional presentation of thought experiments, the event diagram stimulates students to reason with light propagation more explicitly. Like all external representations, event diagrams are a simplified and idealized display of reality and are inherently limited. To wrap up, the authors have shown how their tasks stimulate students to perform thought experiments by drawing light propagation in event diagrams