Institution
University of Fribourg
Education•Fribourg, Freiburg, Switzerland•
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.
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TL;DR: The present results demonstrate the presence of thalamic territories integrating different sensory modalities with motor attributes, and 4 distinct mechanisms of multisensory and sensorimotor interplay are proposed.
Abstract: Multisensory and sensorimotor integrations are usually considered to occur in superior colliculus and cerebral cortex, but few studies proposed the thalamus as being involved in these integrative processes. We investigated whether the organization of the thalamocortical (TC) systems for different modalities partly overlap, representing an anatomical support for multisensory and sensorimotor interplay in thalamus. In 2 macaque monkeys, 6 neuroanatomical tracers were injected in the rostral and caudal auditory cortex, posterior parietal cortex (PE/PEa in area 5), and dorsal and ventral premotor cortical areas (PMd, PMv), demonstrating the existence of overlapping territories of thalamic projections to areas of different modalities (sensory and motor). TC projections, distinct from the ones arising from specific unimodal sensory nuclei, were observed from motor thalamus to PE/PEa or auditory cortex and from sensory thalamus to PMd/PMv. The central lateral nucleus and the mediodorsal nucleus project to all injected areas, but the most significant overlap across modalities was found in the medial pulvinar nucleus. The present results demonstrate the presence of thalamic territories integrating different sensory modalities with motor attributes. Based on the divergent/convergent pattern of TC and corticothalamic projections, 4 distinct mechanisms of multisensory and sensorimotor interplay are proposed.
194 citations
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University Medical Center Freiburg1, University of Freiburg2, Max Planck Society3, University Hospital Regensburg4, University of Zurich5, Goethe University Frankfurt6, Charité7, University of Duisburg-Essen8, University Hospital of Basel9, University of Düsseldorf10, University of Erlangen-Nuremberg11, University Hospital of Giessen and Marburg12, University of Marburg13, University of Fribourg14, Augsburg College15, University of Cologne16, University of Patras17, French Institute of Health and Medical Research18, Utrecht University19, University of Grenoble20, Royal Free Hospital21, Hospital of the University of Pennsylvania22, University of Hamburg23, Vita-Salute San Raffaele University24, Hokkaido University25, German Cancer Research Center26, Technische Universität München27, Princess Margaret Cancer Centre28, University of Minnesota29, Radboud University Nijmegen30, University of Michigan31, Harvard University32, QIMR Berghofer Medical Research Institute33, Royal Brisbane and Women's Hospital34, Fred Hutchinson Cancer Research Center35, University of Cambridge36, University of Texas MD Anderson Cancer Center37, Stanford University38, Sheba Medical Center39, Ohio State University40
TL;DR: Findings indicate that the synergism of T cells and sorafenib is mediated via reduced ATF4 expression, causing activation of the IRF7–IL-15 axis in leukemia cells and thereby leading to metabolic reprogramming of leukemia-reactive T cells in humans.
Abstract: Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD+ leukemia cells. This synergized with the allogeneic CD8+ T cell response, leading to long-term survival in six mouse models of FLT3-ITD+ AML. Sorafenib-related IL-15 production caused an increase in CD8+CD107a+IFN-γ+ T cells with features of longevity (high levels of Bcl-2 and reduced PD-1 levels), which eradicated leukemia in secondary recipients. Mechanistically, sorafenib reduced expression of the transcription factor ATF4, thereby blocking negative regulation of interferon regulatory factor 7 (IRF7) activation, which enhanced IL-15 transcription. Both IRF7 knockdown and ATF4 overexpression in leukemia cells antagonized sorafenib-induced IL-15 production in vitro. Human FLT3-ITD+ AML cells obtained from sorafenib responders following sorafenib therapy showed increased levels of IL-15, phosphorylated IRF7, and a transcriptionally active IRF7 chromatin state. The mitochondrial spare respiratory capacity and glycolytic capacity of CD8+ T cells increased upon sorafenib treatment in sorafenib responders but not in nonresponders. Our findings indicate that the synergism of T cells and sorafenib is mediated via reduced ATF4 expression, causing activation of the IRF7-IL-15 axis in leukemia cells and thereby leading to metabolic reprogramming of leukemia-reactive T cells in humans. Therefore, sorafenib treatment has the potential to contribute to an immune-mediated cure of FLT3-ITD-mutant AML relapse, an otherwise fatal complication after allo-HCT.
193 citations
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TL;DR: Results show that oxygen-independent substrate level phosphorylation either linked to the citric acid cycle or tied into acetate production is essential for growth of procyclic T. brucei, a situation that may reflect an adaptation to the partially hypoxic conditions in the insect host.
193 citations
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TL;DR: In this paper, Covalently cross-linked whey protein microgels (WPMs) were produced without the use of a chemical cross-linking agent, and the hierarchical structure of WPMs is formed by a complex interplay of heat denaturation, aggregation, electrostatic repulsion and formation of disulfide bonds.
Abstract: Covalently cross-linked whey protein microgels (WPM) were produced without the use of a chemical cross-linking agent. The hierarchical structure of WPM is formed by a complex interplay of heat denaturation, aggregation, electrostatic repulsion, and formation of disulfide bonds. Therefore, well-defined spherical particles with a diameter of several hundreds of nanometers and with relatively low polydispersity are formed in a narrow pH regime (5.8–6.2) only. WPM production was carried out on large scale by heating a protein solution in a plate-plate heat exchanger. Thereafter, the microgels were concentrated by microfiltration and spray dried into a powder. The spherical structure of the WPM was conserved in the powder. After re-dispersion, the microgel dispersions fully recovered their initial structure and size distribution. Due to the formation of disulfide bonds the particles were internally covalently cross-linked and were remarkably stable in a large pH range. Because of the pH dependent charge of the constituents the particles underwent significant size changes upon shifting the pH. Small angle X-ray scattering experiments were used to reveal their internal structure, and we report on the pH-induced structural changes occurring on different length scale. Our experiments showed that close analogies could be drawn to internally cross-linked and pH-responsive microgels based on weak polyelectrolytes. WPM also exhibited a pronounced swelling at pH values below the isoelectric point (IEP), and a collapse at the IEP. However, in contrast to classical microgels, WPM are not build up by simple polymer chains but possess a complex hierarchical structure consisting of strands formed by clusters of aggregated denatured proteins that act as primary building blocks. They were flexible enough to respond to changes of the environment, and were stable enough to tolerate pH values where the proteins were highly charged and the strands were stretched.
193 citations
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Finnish Meteorological Institute1, Masaryk University2, Norwegian Meteorological Institute3, Swedish Meteorological and Hydrological Institute4, University of Fribourg5, University of Bern6, Swiss Federal Institute for Forest, Snow and Landscape Research7, Deutscher Wetterdienst8, University of Łódź9
TL;DR: A study of the long-term changes of various climatic extremes was made jointly by a number of European countries as discussed by the authors, which confirmed that the diurnal temperature range has mostly decreased during the present century in Northern and Central Europe.
Abstract: A study of the long-term changes of various climatic extremes was made jointly by a number of European countries. It was found that the changes in maximum and minimum temperatures follow, in broad terms, the corresponding well-documented mean temperature changes. Minimum temperatures, however, have increased slightly more than maximum temperatures, although both have increased. As a result, the study confirms that the diurnal temperature range has mostly decreased during the present century in Northern and Central Europe. Frost has become less frequent. Two extreme-related precipitation characteristics, the annual maximum daily precipitation and the number of days with precipitation greater than or equal to 10 mm, show no major trends or changes in their interannual variability. An analysis of return periods indicated that in the Nordic countries there were high frequencies of 'extraordinary' 1-day rainfalls both in the 1930s and since the 1980s. There have been no long-term changes in the number of high wind speeds in the German Eight. Occurrences of thunderstorms and hails show a decreasing tendency in the Czech Republic during the last 50 years. Finally, using proxy data sources, a 500-year temperature and precipitation event graph for the Swiss Mittelland is presented. It shows large interdecadal variations as well as the exceptionality of the latest decade 1986-1995.
192 citations
Authors
Showing all 6204 results
Name | H-index | Papers | Citations |
---|---|---|---|
Jens Nielsen | 149 | 1752 | 104005 |
Sw. Banerjee | 146 | 1906 | 124364 |
Hans Peter Beck | 143 | 1134 | 91858 |
Patrice Nordmann | 127 | 790 | 67031 |
Abraham Z. Snyder | 125 | 329 | 91997 |
Csaba Szabó | 123 | 958 | 61791 |
Robert Edwards | 121 | 775 | 74552 |
Laurent Poirel | 117 | 621 | 53680 |
Thomas Münzel | 116 | 1055 | 57716 |
David G. Amaral | 112 | 302 | 49094 |
F. Blanc | 107 | 1514 | 58418 |
Markus Stoffel | 102 | 620 | 50796 |
Vincenzo Balzani | 101 | 476 | 45722 |
Enrico Bertini | 99 | 865 | 38167 |
Sandeep Kumar | 94 | 1563 | 38652 |