Inositol 1,4,5- Trisphosphate Receptor Function in Drosophila Insulin Producing Cells

The Inositol 1,4,5- trisphosphate receptor (InsP3R) is an intracellular ligand gated channel that releases calcium from intracellular stores in response to extracellular signals. To identify and understand physiological processes and behavior that depends on the InsP3 signaling pathway at a systemic level, we are studying Drosophila mutants for the InsP3R (itpr) gene. Here, we show that growth defects precede larval lethality and both are a consequence of the inability to feed normally. Moreover, restoring InsP3R function in insulin producing cells (IPCs) in the larval brain rescues the feeding deficit, growth and lethality in the itpr mutants to a significant extent. We have previously demonstrated a critical requirement for InsP3R activity in neuronal cells, specifically in aminergic interneurons, for larval viability. Processes from the IPCs and aminergic domain are closely apposed in the third instar larval brain with no visible cellular overlap. Ubiquitous depletion of itpr by dsRNA results in feeding deficits leading to larval lethality similar to the itpr mutant phenotype. However, when itpr is depleted specifically in IPCs or aminergic neurons, the larvae are viable. These data support a model where InsP3R activity in non-overlapping neuronal domains independently rescues larval itpr phenotypes by non-cell autonomous mechanisms

Interplay between phosphorylation and palmitoylation mediates plasma membrane targeting and sorting of GAP43.

Phosphorylation and lipidation provide posttranslational mechanisms that contribute to the distribution of cytosolic proteins in growing nerve cells. The growth-associated protein GAP43 is susceptible to both phosphorylation and S-palmitoylation and is enriched in the tips of extending neurites. However, how phosphorylation and lipidation interplay to mediate sorting of GAP43 is unclear. Using a combination of biochemical, genetic, and imaging approaches, we show that palmitoylation is required for membrane association and that phosphorylation at Ser-41 directs palmitoylated GAP43 to the plasma membrane. Plasma membrane association decreased the diffusion constant fourfold in neuritic shafts. Sorting to the neuritic tip required palmitoylation and active transport and was increased by phosphorylation-mediated plasma membrane interaction. Vesicle tracking revealed transient association of a fraction of GAP43 with exocytic vesicles and motion at a fast axonal transport rate. Simulations confirmed that a combination of diffusion, dynamic plasma membrane interaction and active transport of a small fraction of GAP43 suffices for efficient sorting to growth cones. Our data demonstrate a complex interplay between phosphorylation and lipidation in mediating the localization of GAP43 in neuronal cells. Palmitoylation tags GAP43 for global sorting by piggybacking on exocytic vesicles, whereas phosphorylation locally regulates protein mobility and plasma membrane targeting of palmitoylated GAP43

The highly potent AhR agonist picoberin modulates Hh-dependent osteoblast differentiation

Identification and analysis of small molecule bioactivity in target-agnostic cellular assays and monitoring changes in phenotype followed by identification of the biological target are a powerful approach for the identification of novel bioactive chemical matter in particular when the monitored phenotype is disease-related and physiologically relevant. Profiling methods that enable the unbiased analysis of compound-perturbed states can suggest mechanisms of action or even targets for bioactive small molecules and may yield novel insights into biology. Here we report the enantioselective synthesis of natural-product-inspired 8-oxotetrahydroprotoberberines and the identification of Picoberin, a low picomolar inhibitor of Hedgehog (Hh)-induced osteoblast differentiation. Global transcriptome and proteome profiling revealed the aryl hydrocarbon receptor (AhR) as the molecular target of this compound and identified a cross talk between Hh and AhR signaling during osteoblast differentiation

Semantics in Support of Biodiversity Knowledge Discovery: An Introduction to the Biological Collections Ontology and Related Ontologies

The study of biodiversity spans many disciplines and includes data pertaining to species distributions and abundances, genetic sequences, trait measurements, and ecological niches, complemented by information on collection and measurement protocols. A review of the current landscape of metadata standards and ontologies in biodiversity science suggests that existing standards such as the Darwin Core terminology are inadequate for describing biodiversity data in a semantically meaningful and computationally useful way. Existing ontologies, such as the Gene Ontology and others in the Open Biological and Biomedical Ontologies (OBO) Foundry library, provide a semantic structure but lack many of the necessary terms to describe biodiversity data in all its dimensions. In this paper, we describe the motivation for and ongoing development of a new Biological Collections Ontology, the Environment Ontology, and the Population and Community Ontology. These ontologies share the aim of improving data aggregation and integration across the biodiversity domain and can be used to describe physical samples and sampling processes (for example, collection, extraction, and preservation techniques), as well as biodiversity observations that involve no physical sampling. Together they encompass studies of: 1) individual organisms, including voucher specimens from ecological studies and museum specimens, 2) bulk or environmental samples (e.g., gut contents, soil, water) that include DNA, other molecules, and potentially many organisms, especially microbes, and 3) survey-based ecological observations. We discuss how these ontologies can be applied to biodiversity use cases that span genetic, organismal, and ecosystem levels of organization. We argue that if adopted as a standard and rigorously applied and enriched by the biodiversity community, these ontologies would significantly reduce barriers to data discovery, integration, and exchange among biodiversity resources and researchers

Propagation of Tau aggregates.

Since 2009, evidence has accumulated to suggest that Tau aggregates form first in a small number of brain cells, from where they propagate to other regions, resulting in neurodegeneration and disease. Propagation of Tau aggregates is often called prion-like, which refers to the capacity of an assembled protein to induce the same abnormal conformation in a protein of the same kind, initiating a self-amplifying cascade. In addition, prion-like encompasses the release of protein aggregates from brain cells and their uptake by neighbouring cells. In mice, the intracerebral injection of Tau inclusions induced the ordered assembly of monomeric Tau, followed by its spreading to distant brain regions. Short fibrils constituted the major species of seed-competent Tau. The existence of several human Tauopathies with distinct fibril morphologies has led to the suggestion that different molecular conformers (or strains) of aggregated Tau exist

Wie wirkt das Miteinanderreden in Psychotherapien aus Sicht von Personen ohne Therapieerfahrung?

Zusammenfassung Hintergrund und Ziel Das Miteinanderreden nimmt in Psychotherapien einen zentralen Raum ein – auch aus Sicht von Personen ohne Therapieerfahrungen. Es ist davon auszugehen, dass Personen ohne Therapieerfahrungen Ideen darüber entwickeln, auf welche Weise das therapeutische Miteinanderreden hilft. Diese Vorstellungen und Vorerwartungen können die therapeutische Interaktion in Psychotherapien beeinflussen. Um ein besseres Verständnis der Erwartungen an Prozesse in der Psychotherapie zu erhalten, soll untersucht werden, welches Bild sich Personen ohne Therapieerfahrungen vom Miteinanderreden in der Psychotherapie machen. Material und Methode Es handelt sich um eine „Mixed-methods“-Studie (qualitative Kategorienbildung mit anschließender quantitativer Häufigkeitsanalyse). An der querschnittlichen Onlineerhebung nahmen 225 Erwachsene ohne Therapie- oder Beratungserfahrung (Alter: Mittelwert [M] = 27,53 Jahre, Standardabweichung [SD] ± 9,93 Jahre, Range 19 bis 91 Jahre, Geschlecht: 207 weiblich, 18 männlich) teil. Neben soziodemografischen Daten wurden Antworten auf die offene Frage: „Wie und auf welche Art und Weise hilft das Miteinanderreden in der Psychotherapie?“ erhoben und inhaltsanalytisch ausgewertet. Ergebnisse Die Teilnehmer:innen erwarteten Wirksamkeit des Miteinanderredens in der Psychotherapie in Bezug auf die 4 Hauptkategorien 1) Therapeutische Beziehung erleben, 2) Erleichterung verschaffen, 3) Erkenntnis gewinnen sowie 4) Veränderungen ermöglichen. Jeder dieser Oberkategorien wurden eine bis 8 Subkategorien zugeordnet. Besonders häufig wurden die Subkategorien „von der Seele reden/Ballast loswerden“ und „Perspektivwechsel“ genannt. Diskussion Die vorliegenden Ergebnisse deuten auf hin, dass Personen ohne Psychotherapieerfahrung differenzierte und jeweils individuell unterschiedliche Annahmen darüber haben, wie das Miteinanderreden in der Psychotherapie heilen kann. Ein Austausch darüber, mit welchen diesbezüglichen Erwartungen Patient:innen in eine Psychotherapie kommen, kann hilfreich sein. </jats:sec