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Institution

Charles University in Prague

EducationPrague, Czechia
About: Charles University in Prague is a education organization based out in Prague, Czechia. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 32392 authors who have published 74435 publications receiving 1804208 citations.


Papers
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Journal ArticleDOI
TL;DR: The data indicate that multiple allosteric interactions between the two subunits are required for wild‐type functioning of the GABAB receptor and highlight further the importance of the dimerization process in GPCR activation.
Abstract: Recent studies on G-protein-coupled receptors revealed that they can dimerize. However, the role of each subunit in the activation process remains unclear. The gamma-amino-n-butyric acid type B (GABA(B)) receptor is comprised of two subunits: GB1 and GB2. Both consist of an extracellular domain (ECD) and a heptahelical domain composed of seven transmembrane alpha-helices, loops and the C-terminus (HD). Whereas GB1 ECD plays a critical role in ligand binding, GB2 is required not only to target GB1 subunit to the cell surface but also for receptor activation. Here, by analysing chimeric GB subunits, we show that only GB2 HD contains the determinants required for G-protein signalling. However, the HD of GB1 improves coupling efficacy. Conversely, although GB1 ECD is sufficient to bind GABA(B) ligands, the ECD of GB2 increases the agonist affinity on GB1, and is necessary for agonist activation of the receptor. These data indicate that multiple allosteric interactions between the two subunits are required for wild-type functioning of the GABA(B) receptor and highlight further the importance of the dimerization process in GPCR activation.

372 citations

Journal ArticleDOI
TL;DR: It is demonstrated that heterozygous MLR mutations cause PHA1, underscore the important role of mineralocorticoid receptor function in regulation of salt and blood pressure homeostasis in humans and motivate further study of this gene for a potential role in blood pressure variation.
Abstract: Pseudohypoaldosteronism type I (PHA1) is characterized by neonatal renal salt wasting with dehydration, hypotension, hyperkalaemia and metabolic acidosis, despite elevated aldosterone levels. Two forms of PHA1 exist. An autosomal recessive form features severe disease with manifestations persisting into adulthood. This form is caused by loss-of-function mutations in genes encoding subunits of the amiloride-sensitive epithelial sodium channel (ENaC; refs 2,3). Autosomal dominant or sporadic PHA1 is a milder disease that remits with age. Among six dominant and seven sporadic PHA1 kindreds, we have found no ENaC gene mutations, implicating mutations in other genes. As ENaC activity in the kidney is regulated by the steroid hormone aldosterone acting through the mineralocorticoid receptor, we have screened the mineralocorticoid receptor gene (MLR) for variants and have identified heterozygous mutations in one sporadic and four dominant kindreds. These include two frameshift mutations (one a de novo mutation), two premature termination codons and one splice donor mutation. These mutations segregate with PHA1 and are not found in unaffected subjects. These findings demonstrate that heterozygous MLR mutations cause PHA1, underscore the important role of mineralocorticoid receptor function in regulation of salt and blood pressure homeostasis in humans and motivate further study of this gene for a potential role in blood pressure variation.

371 citations

Journal ArticleDOI
TL;DR: In this paper, aniline and pyrrole have been oxidized with ammonium peroxydisulfate in aqueous solutions, in the presence of equimolar quantities of hydrochloric acid.

370 citations

Journal ArticleDOI
TL;DR: It is shown that the brains of parrots and songbirds contain on average twice as many neurons as primate brains of the same mass, indicating that avian brains have higher neuron packing densities than mammalian brains.
Abstract: Some birds achieve primate-like levels of cognition, even though their brains tend to be much smaller in absolute size. This poses a fundamental problem in comparative and computational neuroscience, because small brains are expected to have a lower information-processing capacity. Using the isotropic fractionator to determine numbers of neurons in specific brain regions, here we show that the brains of parrots and songbirds contain on average twice as many neurons as primate brains of the same mass, indicating that avian brains have higher neuron packing densities than mammalian brains. Additionally, corvids and parrots have much higher proportions of brain neurons located in the pallial telencephalon compared with primates or other mammals and birds. Thus, large-brained parrots and corvids have forebrain neuron counts equal to or greater than primates with much larger brains. We suggest that the large numbers of neurons concentrated in high densities in the telencephalon substantially contribute to the neural basis of avian intelligence.

370 citations

Journal ArticleDOI
A. Aab1, P. Abreu2, Marco Aglietta3, I. Al Samarai4  +415 moreInstitutions (65)
22 Sep 2017-Science
TL;DR: The Pierre Auger Collaboration reports the observation of thousands of cosmic rays with ultrahigh energies of several exa–electron volts, arriving in a slightly dipolar distribution, showing that they originate outside the Milky Way Galaxy.
Abstract: Cosmic rays are atomic nuclei arriving from outer space that reach the highest energies observed in nature Clues to their origin come from studying the distribution of their arrival directions Using 3 × 10 4 cosmic rays with energies above 8 × 10 18 electron volts, recorded with the Pierre Auger Observatory from a total exposure of 76,800 km 2 sr year, we determined the existence of anisotropy in arrival directions The anisotropy, detected at more than a 52σ level of significance, can be described by a dipole with an amplitude of 65 − 09 + 13 percent toward right ascension α d = 100 ± 10 degrees and declination δ d = − 24 − 13 + 12 degrees That direction indicates an extragalactic origin for these ultrahigh-energy particles

369 citations


Authors

Showing all 32719 results

NameH-indexPapersCitations
Ronald C. Petersen1781091153067
P. Chang1702154151783
Vaclav Vrba141129895671
Milos Lokajicek139151198888
Christopher D. Manning138499147595
Yves Sirois137133495714
Rupert Leitner136120190597
Gerald M. Reaven13379980351
Roberto Sacchi132118689012
S. Errede132148198663
Mark Neubauer131125289004
Peter Kodys131126285267
Panos A Razis130128790704
Vit Vorobel13091979444
Jehad Mousa130122686564
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023203
2022554
20214,838
20204,793
20194,421
20183,991