Institution
University of Tübingen
Education•Tübingen, Germany•
About: University of Tübingen is a education organization based out in Tübingen, Germany. It is known for research contribution in the topics: Population & Immune system. The organization has 40555 authors who have published 84108 publications receiving 3015320 citations. The organization is also known as: Eberhard Karls University & Eberhard-Karls-Universität Tübingen.
Topics: Population, Immune system, Transplantation, Context (language use), Gene
Papers published on a yearly basis
Papers
More filters
••
TL;DR: Molecular mechanisms potentially underlying the memory-enhancing and neuroprotective effects of intranasal insulin are presented and an overview of neuroimaging studies indicating that disturbances in insulin metabolism and altered brain responses to insulin are linked to decreased cerebral volume and especially to hippocampal atrophy is provided.
Abstract: Research in animals and humans has associated Alzheimer’s disease (AD) with decreased cerebrospinal fluid levels of insulin in combination with decreased insulin sensitivity (insulin resistance) in the brain. This phenomenon is accompanied by attenuated receptor expression of insulin and insulin-like growth factor, enhanced serine phosphorylation of insulin receptor substrate-1, and impaired transport of insulin across the blood-brain barrier. Moreover, clinical trials have demonstrated that intranasal insulin improves both memory performance and metabolic integrity of the brain in patients suffering from AD or its prodrome, mild cognitive impairment. These results, in conjunction with the finding that insulin mitigates hippocampal synapse vulnerability to beta amyloid, a peptide thought to be causative in the development of AD, provide a strong rationale for hypothesizing that pharmacological strategies bolstering brain insulin signaling, such as intranasal administration of insulin, could have significant potential in the treatment and prevention of AD. With this view in mind, the review at hand will present molecular mechanisms potentially underlying the memory-enhancing and neuroprotective effects of intranasal insulin. Then, we will discuss the results of intranasal insulin studies that have demonstrated that enhancing brain insulin signaling improves memory and learning processes in both cognitively healthy and impaired humans. Finally, we will provide an overview of neuroimaging studies indicating that disturbances in insulin metabolism—such as insulin resistance in obesity, type 2 diabetes and AD—and altered brain responses to insulin are linked to decreased cerebral volume and especially to hippocampal atrophy.
399 citations
••
TL;DR: The crystal structure of the major histocompatibility complex (MHC) class I homolog, MICA, reveals an NKG2D homodimer bound to a MICA monomer in an interaction that is analogous to that seen in T cell receptor–MHC class I protein complexes.
Abstract: The major histocompatibility complex (MHC) class I homolog, MICA, is a stress-inducible ligand for NKG2D, a C-type lectin−like activating immunoreceptor. The crystal structure of this ligand-receptor complex that we report here reveals an NKG2D homodimer bound to a MICA monomer in an interaction that is analogous to that seen in T cell receptor−MHC class I protein complexes. Similar surfaces on each NKG2D monomer interact with different surfaces on either the α1 or α2 domains of MICA. The binding interactions are large in area and highly complementary. The central section of the α2-domain helix, disordered in the structure of MICA alone, is ordered in the complex and forms part of the NKG2D interface. The extensive flexibility of the interdomain linker of MICA is shown by its altered conformation when crystallized alone or in complex with NKG2D.
399 citations
••
Pasteur Institute1, Leiden University Medical Center2, University of Tübingen3, International Centre for Diarrhoeal Disease Research, Bangladesh4, University of Ibadan5, Mahidol University6, Nangarhar University7, Papua New Guinea Institute of Medical Research8, Walter and Eliza Hall Institute of Medical Research9, University of Melbourne10, Médecins Sans Frontières11, Mbarara University of Science and Technology12, World Health Organization13, Jiangsu University14, National Institute of Parasitic Diseases15, Pennsylvania State University16, Cheikh Anta Diop University17, University of Lomé18, University of Douala19, Research Institute for Tropical Medicine20, Oswaldo Cruz Foundation21, University of Gondar22, Chinese Academy of Sciences23, Henry M. Jackson Foundation for the Advancement of Military Medicine24, Institut de recherche pour le développement25, University of Antwerp26, University of Kinshasa27, Thammasat University28, University of Bamako29, Medical University of Vienna30, Medicines for Malaria Venture31, Université Félix Houphouët-Boigny32, University of London33, Eijkman Institute for Molecular Biology34, Southwest University of Visual Arts35, Columbia University36, Paris Descartes University37
TL;DR: In this article, the authors analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic and identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution.
Abstract: BACKGROUND:
Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale.
METHODS:
We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci.
RESULTS:
We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay.
CONCLUSIONS:
No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).
398 citations
••
TL;DR: CRY overexpression in brain pacemaker cells increases behavioral photosensitivity, and this restricted CRY expression also rescues all circadian defects of cry(b) behavior.
398 citations
••
TL;DR: Motor thresholds varied consistently with changing stimulus parameters, despite substantial interindividual variability, and were consistently higher than the normalized Dantec thresholds by a factor of 1.3.
398 citations
Authors
Showing all 41039 results
Name | H-index | Papers | Citations |
---|---|---|---|
John Q. Trojanowski | 226 | 1467 | 213948 |
Lily Yeh Jan | 162 | 467 | 73655 |
Monique M.B. Breteler | 159 | 546 | 93762 |
Wolfgang Wagner | 156 | 2342 | 123391 |
Thomas Meitinger | 155 | 716 | 108491 |
Hermann Brenner | 151 | 1765 | 145655 |
Amartya Sen | 149 | 689 | 141907 |
Bernhard Schölkopf | 148 | 1092 | 149492 |
Niels Birbaumer | 142 | 835 | 77853 |
Detlef Weigel | 142 | 516 | 84670 |
Peter Lang | 140 | 1136 | 98592 |
Marco Colonna | 139 | 512 | 71166 |
António Amorim | 136 | 1477 | 96519 |
Alexis Brice | 135 | 870 | 83466 |
Elias Campo | 135 | 761 | 85160 |