Levamisole-sensitive acetylcholine receptors (L-AChRs) are ligand-gated ion channels that mediate excitatory neurotransmission at the neuromuscular junctions of nematodes. They constitute a major drug target for anthelminthic treatments because they can be activated by nematode-specific cholinergic agonists such as levamisole. Genetic screens conducted in Caenorhabditis elegans resistance to levamisole toxicity identified genes indispensable biosynthesis L-AChRs. These include 5 encoding...

Abstract Cys-loop neurotransmitter-gated ion channels are vital for communication throughout the nervous system. Following activation, these receptors enter into a desensitized state in which channel shuts even though neurotransmitter molecules remain bound. To date, molecular determinants underlying this most fundamental property of have remained elusive. Here we present generic mechanism desensitization GABA A (GABA Rs) and glycine (GlyRs), both mediate fast inhibitory synaptic...

GABA A receptors (GABA Rs) composed of αβγ subunits are allosterically modulated by the benzodiazepines (BDZs). Agonists at BDZ binding site potentiate submaximal responses increasing apparent affinity Rs for GABA. Although BDZs were initially thought to affect agonists, recent studies suggest an effect on receptor gating; however, involvement preactivation steps in modulation has not been considered. Consequently, we examined whether agonists could exert their modulatory displacing...

Abstract GABA A receptors mediate most inhibitory synaptic transmission in the brain of vertebrates. Following binding and fast activation, these undergo a slower desensitization, conformational pathway which remains largely elusive. To explore mechanism we used concatemeric α1β2γ2 to selectively introduce gain-of-desensitization mutations one subunit at time. library twenty-six mutant combinations was generated their bi-exponential macroscopic desensitization rates measured. Introducing...

Pentameric ligand-gated ion channel mediate signal transduction at chemical synapses by transiting between resting and open states upon neurotransmitter binding. Here, we investigate the gating mechanism of glycine receptor fluorescently labeled extracellular-transmembrane interface voltage-clamp fluorometry (VCF). Fluorescence reports a glycine-elicited conformational change that precedes pore opening. Low concentrations glycine, partial agonists or specific mixtures strychnine trigger full...

Abstract The human α7 nicotinic receptor is a pentameric channel mediating cellular and neuronal communication. It has attracted considerable interest in designing ligands for the treatment of neurological psychiatric disorders. To develop novel class ligands, we recently generated two nanobodies named E3 C4, acting as positive allosteric modulator silent ligand, respectively. Here, solved cryo-electron microscopy structures nanobody-receptor complexes. C4 bind to common epitope involving...

Abstract A comparison was made between two different finishing systems with Belgian Blue bulls. Two groups of bulls were grazed during an initial 140-day period and then finished indoors concentrates. There stocking rates the grazing period: a medium at six per ha (MGFI) high eight (HGFI). third group on concentrate diet whole (FI). The experiment repeated over 2 years consecutively. pasture which rate characterized by higher sward height ( P < 0·01), more refusals 0·001), less Lolium...

Hyperekplexia or startle disease is a serious neurological condition affecting newborn children and usually involves dysfunctional glycinergic neurotransmission. Glycine receptors (GlyRs) are major mediators of inhibition in the spinal cord brainstem. A missense mutation, replacing asparagine (N) with lysine (K), at position 46 GlyR α1 subunit induced hyperekplexia following reduction potency transmitter glycine; this resulted from rapid deactivation agonist current mutant GlyRs. These...

Twelve (Exp. 1) and 24 2) young growing bulls were used to compare the effects of long-acting, cholesterol-based implants with short-acting, lactose-based implants. Each implant contained 200 mg trenbolone acetate 40 17 beta-estradiol. The applied once either 18 wk (early implantation) or 12 (late before slaughter. pellets implanted (6 slaughter), twice (12 6 wk) three times (18, Treated animals had higher live weight gains, a lower feed conversion ratio, proportion lean meat adipose tissue...

The efficacy of GABAergic synapses relies on the number postsynaptic GABAA receptors (GABAARs), which is regulated by a diffusion capture mechanism. Here, we report that conformational state GABAARs influences their membrane dynamics. Indeed, pharmacological and mutational manipulations receptor favoring active or desensitized states altered GABAAR leading to disorganization subsynaptic domains gephyrin scaffold, as detected super-resolution microscopy. Active were confined perisynaptic...

Abstract Pentameric ligand-gated ion channel mediate signal transduction at chemical synapses by transiting between resting and open states upon neurotransmitter binding. Here, we investigate the gating transition of glycine receptor fluorescently labeled extracellular-transmembrane interface voltage-clamp fluorimetry (VCF). Fluorescence reports a glycine-elicited conformational that precedes pore opening. Low concentrations glycine, partial agonists or specific mixtures strychnine trigger...

Resume -Des graines de lin floconn6es sur support d'orge ont 6t6 utilis6es dans une ration pour taurillons I'engraissement.La était a base pulpes séchées et compl6ment6e par l'orge, du tourteau soja des qui représentaient 10% apports.Dans la témoin, été utilise maniere !apporter quantité prot6ine brute semblable !A celle apportée les lin.L'incorporation augmente teneur en extrait ether6 2,1 4,1%.La durée d'engraissement plus longue 5 j chez animaux compl6mentds mati6re grasse.Le gain...

Abstract The human α7 nicotinic receptor is a pentameric channel mediating cellular and neuronal communication. It has attracted considerable interest to design ligands for the treatment of neurological psychiatric disorders. To develop novel class ligands, we recently generated two nanobodies named E3 C4 acting as positive silent allosteric modulators respectively. Here, solved cryo-EM structures nanobody-receptor complexes. bind common epitope involving subunits at apex receptor. They form...

Zusammenfassung Sojaöl in der Jungbullenmast. I. Effekte auf Tierleistung und Schlachtkörperzusammensetzung 12 Jungbullen erhielten eine Kraftfutterration, entweder ohne (Kontrolle) oder mit einem Sojaölsupplement (33 g/kg). Die Sojaölzugabe erhöhte leicht die tägliche Zunahme (1.42 vs 1.40 kg/Tag) erniedrigte Futteraufnahme (1.87 2.01 kg/100 kg Körpermasse/Tag), so daß Futteraufwand verringert war (5.80 6.35 kg/kg). Das Schlachtkörpergewicht betrug 302.6 für Kontrolle 304.4 Sojaölgruppe....

Abstract GABA A receptors mediate most inhibitory synaptic transmission in the brain of vertebrates. Following binding and fast activation, these undergo a slower desensitization, whose conformational pathway remains largely elusive. To explore mechanism we used concatemeric α1β2γ2 to selectively introduce gain-of-desensitization mutations one subunit at time. library twenty-six mutant combinations was generated their bi-exponential macroscopic desensitization rates measured. Introducing...

Zusammenfassung Sojaöl in der Jungbullenmast. II. Effekte auf den Pansenstoffwechsel, die scheinbare Verdaulichkeit und Gehalte am Hormonen Metaboliten im Plasma In zwei Versuchen mit Jungbullen wurde Kraftfutter (33 g/kg) supplementiert. Der Gehalt an Aetherextrakt Sojaölgruppe betrug 57 g/kg Trockensubstanz (T) gegenüber 21 Kontrollgruppe. Im ersten Versuch war eine Tendenz zu niedrigeren Glukose — (10,4 vs. 23,6 mg/l) Ammoniakwerten (73,1 83,1 mg N/l) höheren flüchtige...