University of Fribourg

About: University of Fribourg is a education organization based out in Fribourg, Freiburg, Switzerland. It is known for research contribution in the topics: Population & Context (language use). The organization has 6040 authors who have published 14975 publications receiving 542500 citations. The organization is also known as: UNIFR & Universität Freiburg.

'New' functions for 'old' proteins: the role of the calcium-binding proteins calbindin D-28k, calretinin and parvalbumin, in cerebellar physiology. Studies with knockout mice.

Abstract: Calretinin (CR), calbindin D-28k (CB) and parvalbumin (PV) belong to the large family of EF-hand calcium-binding proteins, which comprises more than 200 members in man. Structurally these proteins are characterized by the presence of a variable number of evolutionary well-conserved helix-loop-helix motives, which bind Ca2+ ions with high affinity. Functionally, they fall into two groups: by interaction with target proteins, calcium sensors translate calcium concentrations into signaling cascades, whereas calcium buffers are thought to modify the spatiotemporal aspects of calcium transients. Although CR, CB and PV are currently being considered calcium buffers, this may change as we learn more about their biology. Remarkable differences in their biophysical properties have led to the distinction of fast and slow buffers and suggested functional specificity of individual calcium buffers. Evaluation of the physiological roles of CR, CB and PV has been facilitated by the recent generation of mouse strains deficient in these proteins. Here, we review the biology of these calcium-binding proteins with distinct reference to the cerebellum, since they are particularly enriched in specific cerebellar neurons. CR is principally expressed in granule cells and their parallel fibres, while PV and CB are present throughout the axon, soma, dendrites and spines of Purkinje cells. PV is additionally found in a subpopulation of inhibitory interneurons, the stellate and basket cells. Studies on deficient mice together with in vitro work and their unique cell type-specific distribution in the cerebellum suggest that these calcium-binding proteins have evolved as functionally distinct, physiologically relevant modulators of intracellular calcium transients. Analysis of different brain regions suggests that these proteins are involved in regulating calcium pools critical for synaptic plasticity. Surprisingly, a major role of any of these three calcium-binding proteins as an endogenous neuroprotectant is not generally supported.

Brain Size Predicts the Success of Mammal Species Introduced into Novel Environments

Abstract: Large brains, relative to body size, can confer advantages to individuals in the form of behavioral flexibility Such enhanced behavioral flexibility is predicted to carry fitness benefits to individuals facing novel or altered environmental conditions, a theory known as the brain size-environmental change hypothesis Here, we provide the first empirical link between brain size and survival in novel environments in mammals, the largest-brained animals on Earth Using a global database documenting the outcome of more than 400 introduction events, we show that mammal species with larger brains, relative to their body mass, tend to be more successful than species with smaller brains at establishing themselves when introduced to novel environments, when both taxonomic and regional autocorrelations are accounted for This finding is robust to the effect of other factors known to influence establishment success, including introduction effort and habitat generalism Our results replicate similar findings in birds, increasing the generality of evidence for the idea that enlarged brains can provide a survival advantage in novel environments

Predicting Homework Effort: Support for a Domain-Specific, Multilevel Homework Model.

Abstract: According to the domain-specific, multilevel homework model proposed in the present study, students' homework effort is influenced by expectancy and value beliefs, homework characteristics, parental homework behavior, and conscientiousness. The authors used structural equation modeling and hierarchical linear modeling analyses to test the model in 2 studies with 414 and 1,501 8th graders, respectively. In line with the authors' assumptions, most intercorrelations observed between corresponding homework variables across 2 school subjects were small to moderate, conscientiousness and homework motivation proved to be strong predictors of homework effort, and perceived homework quality varied considerably between classes and predicted homework motivation and behavior. Findings highlight the need to take into account the domain specificity and multilevel character of homework variables when analyzing students' homework behavior.

Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages

Abstract: Precise knowledge regarding cellular uptake of nanoparticles is of great importance for future biomedical applications. Four different endocytotic uptake mechanisms, that is, phagocytosis, macropinocytosis, clathrin- and caveolin-mediated endocytosis, were investigated using a mouse macrophage (J774A.1) and a human alveolar epithelial type II cell line (A549). In order to deduce the involved pathway in nanoparticle uptake, selected inhibitors specific for one of the endocytotic pathways were optimized regarding concentration and incubation time in combination with fluorescently tagged marker proteins. Qualitative immunolocalization showed that J774A.1 cells highly expressed the lipid raft-related protein flotillin-1 and clathrin heavy chain, however, no caveolin-1. A549 cells expressed clathrin heavy chain and caveolin-1, but no flotillin-1 uptake-related proteins. Our data revealed an impeded uptake of 40 nm polystyrene nanoparticles by J774A.1 macrophages when actin polymerization and clathrin-coated pit formation was blocked. From this result, it is suggested that macropinocytosis and phagocytosis, as well as clathrin-mediated endocytosis, play a crucial role. The uptake of 40 nm nanoparticles in alveolar epithelial A549 cells was inhibited after depletion of cholesterol in the plasma membrane (preventing caveolin-mediated endocytosis) and inhibition of clathrin-coated vesicles (preventing clathrin-mediated endocytosis). Our data showed that a combination of several distinguishable endocytotic uptake mechanisms are involved in the uptake of 40 nm polystyrene nanoparticles in both the macrophage and epithelial cell line.

Deciphering protein kinase specificity through large-scale analysis of yeast phosphorylation site motifs

Abstract: Phosphorylation is a universal mechanism for regulating cell behavior in eukaryotes. Although protein kinases target short linear sequence motifs on their substrates, the rules for kinase substrate recognition are not completely understood. We used a rapid peptide screening approach to determine consensus phosphorylation site motifs targeted by 61 of the 122 kinases in Saccharomyces cerevisiae. By correlating these motifs with kinase primary sequence, we uncovered previously unappreciated rules for determining specificity within the kinase family, including a residue determining P-3 arginine specificity among members of the CMGC [CDK (cyclin-dependent kinase), MAPK (mitogen-activated protein kinase), GSK (glycogen synthase kinase), and CDK-like] group of kinases. Furthermore, computational scanning of the yeast proteome enabled the prediction of thousands of new kinase-substrate relationships. We experimentally verified several candidate substrates of the Prk1 family of kinases in vitro and in vivo and identified a protein substrate of the kinase Vhs1. Together, these results elucidate how kinase catalytic domains recognize their phosphorylation targets and suggest general avenues for the identification of previously unknown kinase substrates across eukaryotes.