TOI-836 : a super-Earth and mini-Neptune transiting a nearby K-dwarf

Funding: TGW, ACC, and KH acknowledge support from STFC consolidated grant numbers ST/R000824/1 and ST/V000861/1, and UKSA grant ST/R003203/1.We present the discovery of two exoplanets transiting TOI-836 (TIC 440887364) using data from TESS Sector 11 and Sector 38. TOI-836 is a bright (T = 8.5 mag), high proper motion (∼200 mas yr−1), low metallicity ([Fe/H]≈−0.28) K-dwarf with a mass of 0.68 ± 0.05 M⊙ and a radius of 0.67 ± 0.01 R⊙. We obtain photometric follow-up observations with a variety of facilities, and we use these data-sets to determine that the inner planet, TOI-836 b, is a 1.70 ± 0.07 R⊕ super-Earth in a 3.82 day orbit, placing it directly within the so-called ‘radius valley’. The outer planet, TOI-836 c, is a 2.59 ± 0.09 R⊕ mini-Neptune in an 8.60 day orbit. Radial velocity measurements reveal that TOI-836 b has a mass of 4.5 ± 0.9 M⊕, while TOI-836 c has a mass of 9.6 ± 2.6 M⊕. Photometric observations show Transit Timing Variations (TTVs) on the order of 20 minutes for TOI-836 c, although there are no detectable TTVs for TOI-836 b. The TTVs of planet TOI-836 c may be caused by an undetected exterior planet.Publisher PDFPeer reviewe

TOI-836: A super-Earth and mini-Neptune transiting a nearby K-dwarf

We present the discovery of two exoplanets transiting TOI-836 (TIC 440887364) using data from TESS Sector 11 and Sector 38. TOI-836 is a bright ($T = 8.5$ mag), high proper motion ($\sim\,200$ mas yr$^{-1}$), low metallicity ([Fe/H]$\approx\,-0.28$) K-dwarf with a mass of $0.68\pm0.05$ M$_{\odot}$ and a radius of $0.67\pm0.01$ R$_{\odot}$. We obtain photometric follow-up observations with a variety of facilities, and we use these data-sets to determine that the inner planet, TOI-836 b, is a $1.70\pm0.07$ R$_{\oplus}$ super-Earth in a 3.82 day orbit, placing it directly within the so-called 'radius valley'. The outer planet, TOI-836 c, is a $2.59\pm0.09$ R$_{\oplus}$ mini-Neptune in an 8.60 day orbit. Radial velocity measurements reveal that TOI-836 b has a mass of $4.5\pm0.9$ M$_{\oplus}$ , while TOI-836 c has a mass of $9.6\pm2.6$ M$_{\oplus}$. Photometric observations show Transit Timing Variations (TTVs) on the order of 20 minutes for TOI-836 c, although there are no detectable TTVs for TOI-836 b. The TTVs of planet TOI-836 c may be caused by an undetected exterior planet

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

TOI-836: A super-Earth and mini-Neptune transiting a nearby K-dwarf

peer reviewe

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Identification et caractérisation des sous-unités ELP5 et ELP6 du complexe Elongator humain

Familial Dysautonomia is a neurodegenerative disorder that affects the autonomic and sensory nervous systems. This disease results from loss-of-function mutations of the ELP1-encoding gene. ELP1 is required for the integrity of the so-called Elongator complex, which is composed of two sub-proteins complexes, namely the core-Elongator (ELP1 to ELP3) and HAP (ELP4 to ELP6). While ELP3 is acting as an acetyltransferase that target multiple substrates such as nuclear histones and cytoplasmic α-tubulin, the ELP4-6 has been recently described as an ATPase. This complex has been initially identified as a component of a hyperphosphorylated RNA polymerase II holoenzyme. As a result, Elongator is involved in transcriptional elongation. Since, other roles have been assigned. Elongator is indeed also required for some tRNA modifications in the cytoplasm and consequently controls translation fidelity. Those molecular functions underlie the capacity of Elongator to regulate cell division, DNA-damage response and cell motility. It is likely that a better understanding of the molecular functions of Elongator will clarify its role in these cellular processes and probably highlight new features. The identity of human ELP1 through ELP4 has been reported but human ELP5 and ELP6 have remained uncharacterized. We therefore initiated a study dedicated to the identification and characterization of both proteins. A biochemical purification of ELP4 was conducted to isolate all associated proteins. Such experimental approach led to the identification of DERP6 and C3ORF75 as human ELP5 and ELP6 subunits of the Elongator complex, respectively. We further investigated the cellular functions of both subunits by combining biochemical analysis and cellular assays. Our results show that DERP6/Elp5 is required for the integrity and the fucntion of Elongator and directly connects ELP3 to ELP4. Our laboratory has previously demonstrated the key role of Elongator in cell migration. As cell motility is required for cell invasion and metastasis, we therefore investigated to which extent Elongator is involved in those processes. The migration and tumorigenicity of melanoma-derived cells are significantly decreased upon Elongator invalidation through Elp1 or Elp3 depletion. Strikingly, DERP6/Elp5 and C3ORF75/Elp6-depleted melanoma cells have similar defects, further supporting the idea that DERP6/Elp5 and C3ORF75/Elp6 are essential for Elongator function. Together, our data identify DERP6/ELP5 and C3ORF75/ELP6 as key players for migration, invasion and tumorigenicity of melanoma cells, as integral subunits of Elongator.La dysautonomie familiale est une pathologie neurodégénérative qui touche les systèmes nerveux sensoriel et autonome. Cette maladie résulte de mutations de perte de fonction du gène codant pour la protéine ELP1. Celle-ci permet l’assemblage d’Elongator, un complexe doué d’une activité acétyltransférase et composé de six sous-unités réparties en deux sous-complexes protéiques : d’une part le « core-Elongator » (ELP1 à ELP3) et d’autre part le complexe HAP (ELP4 à ELP6). Alors que la sous-unité ELP3 est capable d’acétyler de nombreux substrats dont les histones nucléaires et la tubuline-α cytoplasmique, une activité ATPase a récemment été identifiée dans le complexe ELP4-6. Initialement identifié sur base de son association à l’ARN polymérase II, Elongator a depuis été caractérisé comme un acteur important de l’acétylation des microtubules, de même que comme complexe requis pour certaines modifications des ARNs de transfert. Ces fonctions moléculaires très diverses lui confèrent la capacité de réguler de nombreux processus physiologiques tels que la division ou la migration cellulaire. Une meilleure connaissance des fonctions moléculaires d’Elongator permettrait non seulement d’éclaircir son rôle dans ces différents processus cellulaires mais également de révéler de nouvelles fonctions. Au moment d’entamer nos travaux, l’identité des sous-unités humaines ELP1, 2, 3 et 4 était connue, à l’inverse des sous-unités ELP5 et ELP6. Nous avons donc entrepris d’identifier et de caractériser ces deux protéines. La purification de la protéine ELP4 humaine nous a permis d’isoler le complexe Elongator dans son intégralité. Ainsi, nous avons pu identifier les protéines DERP6 et C3ORF75 comme étant respectivement les sous-unités ELP5 et ELP6 du complexe Elongator humain. Nous avons en outre démontré qu’ELP5 est indispensable pour permettre l’association entre ELP3 et à ELP4, ceci suggérant qu’ELP5 est également requis pour l’intégrité et la fonction d’Elongator. Notre laboratoire a précédemment mis en évidence l’importance d’Elongator dans la migration cellulaire. Compte-tenu du fait que la migration est une étape critique dans l’acquisition du pouvoir invasif et métastatique des cellules cancéreuses, nous avons voulu déterminer dans quelle mesure Elongator intervenait dans ces processus physiopathologiques en étudiant une lignée dérivée de mélanome murin à titre de modèle expérimental. La perte de fonction d’Elongator altère la mobilité de ces cellules de même que leur capacité à former des colonies en agar mou. Les mêmes résultats ont été obtenus en invalidant les sous-unités Elp5 et Elp6 nouvellement identifiées dans ces cellules murines. L’ensemble de nos résultats montre qu’Elongator est requis pour la migration et la tumorigénicité des cellules cancéreuses issues de mélanome murin et que les sous-unités DERP6/ELP5 et C3ORF75/ELP6 confèrent ces propriétés cellulaires en tant que sous-unités de ce complexe

Muscarinic receptor heterogeneity in rat central nervous system. II. Brain receptors labeled by [3H]oxotremorine-M correspond to heterogeneous M2 receptors with very high affinity for agonists

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

In vitro effects of gallamine on dissociation kinetics of (3H)N-methylscopolamine and (3H)pirenzepine from rat brain muscarinic receptors

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Kinetic studies of [3H]-N-methylscopolamine binding to muscarinic receptors in the rat central nervous system: evidence for the existence of three classes of binding sites.

We compared the binding of [N-methyl-3H]scopolamine methyl chloride [( 3H]NMS) and pirenzepine to muscarinic receptors in four regions of the rat central nervous system (cortex, hippocampus, striatum, and cerebellum) and in rat heart. Equilibrium binding studies suggested the existence of three classes of receptors: A, receptors with high affinity for pirenzepine and [3H] NMS (in cortex, hippocampus, and striatum); B, receptors with intermediate affinity for pirenzepine and high affinity for [3H]NMS (in the same brain regions); and C, receptors with low affinity for pirenzepine and [3H]NMS (in cerebellum and heart). Dissociation kinetic studies indicated that the receptor types A, B, and C had different koff values allowing, therefore, a separate study of their binding properties. We observed that: [3H]NMS recognized muscarinic receptors A, B, and C with the following order of potency: B greater than A much greater than C; and pirenzepine recognized these receptors with a different order of potency: A much greater than B greater than C. Thus, dissociation kinetics provide a useful tool to identify muscarinic receptor types.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

Muscarinic receptor heterogeneity in rat central nervous system. I. Binding of four selective antagonists to three muscarinic receptor subclasses: a comparison with M2 cardiac muscarinic receptors of the C type.

We previously observed that [3H]NMS recognizes three types of muscarinic receptors in rat brain (one M1 subclass with high affinity for pirenzepine, and two M2 subclasses with low affinities for pirenzepine), based on distinct affinity and kinetic constants of [3H]NMS for these three subclasses. In this work, we investigated the binding of four selective antagonists to these three (the M1 and two M2) subclasses. We were able to demonstrate that cardiac-like M2 receptors with low affinity for pirenzepine and low affinity for N-methylscopolamine were present not only in cerebellum (as previously shown; see introduction) but also in cortex, striatum, and hippocampus, and the two M2 receptor subclasses were discriminated by dicyclomine, 4-DAMP, and gallamine, as well as by AF-DX 116 and [3H]NMS. Our findings also suggested that the biphasic association and dissociation kinetics of [3H]NMS observed in various brain regions reflect sequential binding to the different receptors.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe