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In the adult human brain, six isoforms of the microtubule-associated protein TAU are expressed, which result from alternative splicing of exons 2, 3, and 10 of the MAPT gene. These isoforms differ in the number of N-terminal inserts (0N, 1N, 2N) and C-terminal repeat domains (3R or 4R) and are differentially expressed depending on the brain region and developmental stage. Although all TAU isoforms can aggregate and form neurofibrillary tangles, some tauopathies, such as Pick's disease and progressive supranuclear palsy, are characterized by the accumulation of specific TAU isoforms. The influence of the individual TAU isoforms in a cellular context, however, is understudied. In this report, we investigated the subcellular localization of the human-specific TAU isoforms in primary mouse neurons and analyzed TAU isoform-specific effects on cell area and microtubule dynamics in human SH-SY5Y neuroblastoma cells. Our results show that 2N-TAU isoforms are particularly retained from axonal sorting and that axonal enrichment is independent of the number of repeat domains, but that the additional repeat domain of 4R-TAU isoforms results in a general reduction of cell size and an increase of microtubule counts in cells expressing these specific isoforms. Our study points out that individual TAU isoforms may influence microtubule dynamics differentially both by different sorting patterns and by direct effects on microtubule dynamics.Creativity is commonly defined as a process that leads to a novel and useful outcome (an idea, product, or expression). However, two dilemmas about this definition remain unresolved (1) A strict application of usefulness is difficult to apply to artistic works who decides what artwork is useful, and how it is useful? (2) The implied boundary conditions of novelty are problematic The default perspective is that novelty has a monotonic increasing relationship with creativity, or it is categorical-i.e., novel or not. To address these dilemmas, this paper proposes a spreading activation model of creativity (SAMOC), a model built on a brain-architecture-inspired vast interconnected network of nodes, each node representing information, and assigned meanings through interaction with the environment. Nodes are linked to each other according to principles of temporal contiguity (linking objects/events in time) and similarity (linking objects/events by shared features). Selleck HG-9-91-01 A node activated by attention spreads through thelications for future empirical research programs on creativity, and for the definition of creativity itself.Immunostaining is a powerful technique and widely used to identify molecules in tissues and cells, although critical steps are necessary to block cross-reaction. Here we focused on an overlooked cross immunoreactivity issue where a secondary antibody (secondary) cross-reacts with a primary antibody (primary) from a different species. We first confirmed the previously reported cross-species binding of goat anti-mouse secondary to rat primary. This was accomplished by staining with a rat primary against glial fibrillary acidic protein (GFAP) and visualizing with goat (or donkey) anti-mouse secondary. We then further revealed the converse cross-species binding by staining with a mouse primary against neuronal nuclear protein (NeuN) and visualizing with anti-rat secondaries. We speculate that mouse and rat primaries share antigenicity, enabling either secondary to recognize either primary. To block this cross-species binding in double staining experiments, we compared three protocols using mouse anti-NeuN and rat anti-GFAP, two primaries whose antigens have non-overlapping distributions in brain tissues. Simultaneous staining resulted in cross-species astrocytic staining (anti-mouse secondary to rat anti-GFAP primary) but no cross-species neuronal staining (anti-rat secondary to mouse anti-NeuN primary). Cross-species astrocytic staining was missing after sequential same-species staining with mouse anti-NeuN primary, followed by rat anti-GFAP. However, cross-species astrocytic staining could not be diminished after sequential same-species staining with rat anti-GFAP primary, followed by mouse anti-NeuN. We thus hypothesize that a competition exists between anti-mouse and anti-rat secondaries in their binding to both primaries. Single staining for NeuN or GFAP visualized with dual secondaries at different dilution ratio supported this hypothesis.Prediction of successful memory encoding is important for learning. High-frequency activity (HFA), such as gamma frequency activity (30-150 Hz) of cortical oscillations, is induced during memory tasks and is thought to reflect underlying neuronal processes. Previous studies have demonstrated that medio-temporal electrophysiological characteristics are related to memory formation, but the effects of neocortical neural activity remain underexplored. The main aim of the present study was to evaluate the ability of gamma activity in human electrocorticography (ECoG) signals to differentiate memory processes into remembered and forgotten memories. A support vector machine (SVM) was employed, and ECoG recordings were collected from six subjects during verbal memory recognition task performance. Two-class classification using an SVM was performed to predict subsequently remembered vs. forgotten trials based on individually selected frequencies (low gamma, 30-60 Hz; high gamma, 60-150 Hz) at time points during pre- and during stimulus intervals. The SVM classifier distinguished memory performance between remembered and forgotten trials with a mean maximum accuracy of 87.5% using temporal cortical gamma activity during the 0- to 1-s interval. Our results support the functional relevance of ECoG for memory formation and suggest that lateral temporal cortical HFA may be utilized for memory prediction.

Care transitions between specialist and primary healthcare services for people with concurrent substance abuse and mental health problems are characterised by vulnerability and arbitrariness.

By studying factors that influence integration in a Norwegian context, this study aims to investigate, from a municipal perspective, why care transitions are still tricky after the introduction of the key Coordination Reform.

This study has an explorative approach based on interviews with managers and front-line professionals in primary care. We applied the conceptual framework of functional and normative integration of the Rainbow Model.

The municipal actors emphasise that integration is hampered by limited cooperation with general practitioners in referrals to hospital, challenges of communication and loss of meeting points. They experienced close cooperation with sociomedical polyclinics for substance abuse, while challenges in cooperation with district psychiatric centres indicated an interdependence of functional and normative integration.

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