Institution
University of Lausanne
Education•Lausanne, Switzerland•
About: University of Lausanne is a education organization based out in Lausanne, Switzerland. It is known for research contribution in the topics: Population & Medicine. The organization has 20508 authors who have published 46458 publications receiving 1996655 citations. The organization is also known as: Université de Lausanne & UNIL.
Topics: Population, Medicine, Context (language use), Gene, Immune system
Papers published on a yearly basis
Papers
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TL;DR: New types of ΨPro building blocks suitable for standard Fmoc/tBu-based solid phase peptide synthesis, convergent strategies, and chemoselective ligation techniques are described as well as their use as a structure-disrupting, solubilizing protection technique for the e- peptide assembly.
Abstract: Serine-, threonine-, and cysteine-derived cyclic building blocks (pseudo-prolines, ΨPro) serve as reversible protecting groups for Ser, Thr, and Cys and prove to be versatile tools for overcoming some intrinsic problems in the field of peptide chemistry. The presence of ΨPro within a peptide sequence results in the disruption of β-sheet structures considered as a source of intermolecular aggregation during chain elongation, thus increasing solvation and coupling kinetics in peptide assembly. Due to their easy synthetic access and variability in the chemical stability by modifications introduced in the C-2 position of the oxazolidine/thiazolidine ring system, this protection technique is adaptable to all common strategies in peptide synthesis. We describe new types of ΨPro building blocks suitable for standard Fmoc/tBu-based solid phase peptide synthesis, convergent strategies, and chemoselective ligation techniques as well as their use as a structure-disrupting, solubilizing protection technique for the e...
332 citations
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Marcel den Hoed1, Mark Eijgelsheim2, Tõnu Esko3, Bianca J. J. M. Brundel4 +264 more•Institutions (85)
TL;DR: A 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci, providing fresh insights into the mechanisms regulating heart rate.
Abstract: Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.
332 citations
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TL;DR: Patients receiving nonnucleoside reverse-transcriptase inhibitors had higher levels of TC and LDL-c than did antiretroviral-naive patients, although the risk of having lower HDL-c levels was lower than that in patients receiving a single PI.
Abstract: Levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c), as well as the TC:HDL-c ratio, were compared in patients receiving different antiretroviral therapy regimens. Patients receiving first-line regimens including protease inhibitors (PIs) had higher TC and TG levels and TC : HDL-c ratios than did antiretroviral-naive patients; patients receiving 2 PIs had higher levels of each lipid. Ritonavir-containing regimens were associated with higher TC and TG levels and TC : HDL-c ratios than were indinavir-containing regimens; however, receipt of nelfinavir was associated with reduced risk of lower HDL-c levels, and receipt of saquinavir was associated with lower TC : HDL-c ratios. Patients receiving nonnucleoside reverse-transcriptase inhibitors had higher levels of TC and LDL-c than did antiretroviral-naive patients, although the risk of having lower HDL-c levels was lower than that in patients receiving a single PI. Efavirenz was associated with higher levels of TC and TG than was nevirapine.
332 citations
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University Hospital Bonn1, University of Miami2, All India Institute of Medical Sciences3, University of the Witwatersrand4, University of Texas MD Anderson Cancer Center5, University of Panama6, Kenyatta National Hospital7, University of Navarra8, Indiana University9, Mongolian National University10, King's College London11, University of Lausanne12, Makerere University13, American University of Beirut14, George Washington University15, University of Oxford16, Catholic University of Korea17
TL;DR: The greatest challenge faced by the core group was trying to find a middle ground between those who think that PC is the relief of all suffering and those who believe that PC describes the care of those with a very limited remaining life span.
332 citations
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TL;DR: In this paper, the effects of pneumolysin on Dendritic cells (DC) were investigated and it was shown that PLY-induced DC maturation and cytokine secretion by DC and splenocytes was TLR4-independent.
Abstract: Pneumolysin (PLY) is a key Streptococcus pneumoniae virulence factor and potential candidate for inclusion in pneumococcal subunit vaccines. Dendritic cells (DC) play a key role in the initiation and instruction of adaptive immunity, but the effects of PLY on DC have not been widely investigated. Endotoxin-free PLY enhanced costimulatory molecule expression on DC but did not induce cytokine secretion. These effects have functional significance as adoptive transfer of DC exposed to PLY and antigen resulted in stronger antigen-specific T cell proliferation than transfer of DC exposed to antigen alone. PLY synergized with TLR agonists to enhance secretion of the proinflammatory cytokines IL-12, IL-23, IL-6, IL-1β, IL-1α and TNF-α by DC and enhanced cytokines including IL-17A and IFN-γ by splenocytes. PLY-induced DC maturation and cytokine secretion by DC and splenocytes was TLR4-independent. Both IL-17A and IFN-γ are required for protective immunity to pneumococcal infection and intranasal infection of mice with PLY-deficient pneumococci induced significantly less IFN-γ and IL-17A in the lungs compared to infection with wild-type bacteria. IL-1β plays a key role in promoting IL-17A and was previously shown to mediate protection against pneumococcal infection. The enhancement of IL-1β secretion by whole live S. pneumoniae and by PLY in DC required NLRP3, identifying PLY as a novel NLRP3 inflammasome activator. Furthermore, NLRP3 was required for protective immunity against respiratory infection with S. pneumoniae. These results add significantly to our understanding of the interactions between PLY and the immune system.
332 citations
Authors
Showing all 20911 results
Name | H-index | Papers | Citations |
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Peer Bork | 206 | 697 | 245427 |
Aaron R. Folsom | 181 | 1118 | 134044 |
Kari Alitalo | 174 | 817 | 114231 |
Ralph A. DeFronzo | 160 | 759 | 132993 |
Johan Auwerx | 158 | 653 | 95779 |
Silvia Franceschi | 155 | 1340 | 112504 |
Matthias Egger | 152 | 901 | 184176 |
Bart Staels | 152 | 824 | 86638 |
Fernando Rivadeneira | 146 | 628 | 86582 |
Christopher George Tully | 142 | 1843 | 111669 |
Richard S. J. Frackowiak | 142 | 309 | 100726 |
Peter Timothy Cox | 140 | 1267 | 95584 |
Jürg Tschopp | 140 | 328 | 86900 |
Stylianos E. Antonarakis | 138 | 746 | 93605 |
Michael Weller | 134 | 1105 | 91874 |