Search results for "M5"

Synthesis and Muscarinic Activity of Isoxazole-substituted 1,2,5,6-Tetrahydropyridines

1994

RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis.

2012

The function of cytosine-C5 methylation, a widespread modification of tRNAs, has remained obscure, particularly in mammals. We have now developed a mouse strain defective in cytosine-C5 tRNA methylation, by disrupting both the Dnmt2 and the NSun2 tRNA methyltransferases. Although the lack of either enzyme alone has no detectable effects on mouse viability, double mutants showed a synthetic lethal interaction, with an underdeveloped phenotype and impaired cellular differentiation. tRNA methylation analysis of the double-knockout mice demonstrated complementary target-site specificities for Dnmt2 and NSun2 and a complete loss of cytosine-C5 tRNA methylation. Steady-state levels of unmethylate…

Further Delineation of Duplications of ARX Locus Detected in Male Patients with Varying Degrees of Intellectual Disability

2022

The X-linked gene encoding aristaless-related homeobox (ARX) is a bi-functional transcription factor capable of activating or repressing gene transcription, whose mutations have been found in a wide spectrum of neurodevelopmental disorders (NDDs); these include cortical malformations, paediatric epilepsy, intellectual disability (ID) and autism. In addition to point mutations, duplications of the ARX locus have been detected in male patients with ID. These rearrangements include telencephalon ultraconserved enhancers, whose structural alterations can interfere with the control of ARX expression in the developing brain. Here, we review the structural features of 15 gain copy-number variants …

Monsoon onset over Sudan-Sahel: Simulation by the regional scale model MM5.

2006

[1] The Mesoscale Model MM5 is used to study the regional features of the West African Monsoon onset. In order to increase the results, simulations are carried out for eight consecutive seasons (March to September) of the years 1994 to 2001. The results show that the model can reproduce the dynamical features of the monsoon in a reasonably good manner but the seasonal cycle seems enhanced. It is hypothesized that overestimated rainfall amounts could be related to a poor representation of the land surface characteristics. Nevertheless, the mean simulated monsoon onset dates are similar to those find in the CMAP data set. The onset is characterized by an apparent increase in zonal flow that c…

Structural and Functional Analysis of BBA03, Borrelia burgdorferi Competitive Advantage Promoting Outer Surface Lipoprotein

2020

BBA03 is a Borrelia burgdorferi outer surface lipoprotein encoded on one of the most conserved plasmids in Borrelia genome, linear plasmid 54 (lp54). Although many of its genes have been identified as contributing or essential for spirochete fitness in vivo, the majority of the proteins encoded on this plasmid have no known function and lack homologs in other organisms. In this paper, we report the solution NMR structure of the B. burgdorferi outer surface lipoprotein BBA03, which is known to provide a competitive advantage to the bacteria during the transmission from tick vector to mammalian host. BBA03 shows structural homology to other outer surface lipoproteins reflecting their genetic …

Cell signaling mechanisms of oro-gustatory detection of dietary fat: Advances and challenges

2013

CD36 and two G-protein coupled receptors (GPCR), i.e., GPR120 and GPR40, have been implicated in the gustatory perception of dietary fats in rodents. These glycoproteins are coupled to increases in free intracellular Ca²⁺ concentrations, [Ca²⁺](i), during their activation by dietary long-chain fatty acids (LCFA). The transient receptor potential type M5 (TRPM5) channel, activated by [Ca²⁺](i), participates in downstream signaling in taste bud cells (TBC). The mice, knocked-out for expression of CD36, GPR120, GPR40 or TRPM5 have a reduced spontaneous preference for fat. The delayed rectifying K⁺ (DRK) channels believed to lie downstream of these receptors are also important players in fat ta…

Attivisti 5 Stelle a Palermo

2015

Nel 2005 nasce il primo Meetup palermitano, alla protesta contro i partiti unisce l’impegno ambientalista. Nel 2012 alle comunali la lista civica del Movimento 5 Stelle non raggiunge il 5%, ma diventa primo partito alle regionali (14,9%). Gli attivisti intervistati raccontano le diverse fasi del movimento a Palermo, tra successi e periodi critici. In 2005 the first Meetup arose in Palermo in order to protest against political parties and to support environmental issues. In 2012 the municipal civic list 5 Star Movement did not reach 5%, but it became the first party at the regional elections (14.9%). The interviewed activists illustrate the different stages of the movement in Palermo, descri…

Muscarinic modulation of acetylcholine release: Receptor subtypes and possible mechanisms

1989

The release of acetylcholine from central and peripheral neurones can be inhibited and facilitated by muscarine autoreceptors, i.e. receptors located on the cholinergic neurone. In the last few years evidence has accumulated that muscarine receptors are heterogeneous. This chapter describes attempts that have been made to classify the muscarine autoreceptors. In addition, some possible mechanisms behind the neuronal muscarine receptors are examined.

Highly sensitive monoclonal antibody-based immunoassays for boscalid analysis in strawberries

2018

Boscalid is an agrochemical recently developed for crop protection and the most significant member of the succinate dehydrogenase inhibitor group of fungicides. In this study, a collection of high-affinity monoclonal antibodies was generated to boscalid. By using a series of haptens with a linker at alternative tethering sites of the boscalid framework, specific antibodies were isolated as well as antibodies that also recognized the main boscalid metabolite. Two immunoassays were developed using different ELISA formats. Optimized assays displayed very high sensitivities (limits of detection were near 0.01 µg/L). Trueness and precision for the determination of the target analyte in strawberr…

Desensitization is a property of the cholinergic binding region of the nicotinic acetylcholine receptor, not of the receptor-integral ion channel

1991

AbstractThe reversible acetylcholine esterase inhibitor (−)-physostigmine (eserine) is the prototype of a new class of nicotinic acetylcholine receptor (nAChR) activating ligands: it induces cation fluxes into nAChR-rich membrane vesicles from Torpedo marmorala electric tissue even under conditions of antagonist blocked acetylcholine binding sites (Okonjo, Kuhlmann, Maclicke, Neuron, in press). This suggests that eserine exerts its channel-activating property via binding sites at the nAChR separate from those of the natural transmitter. We now report that eserine can activate the channel even when the receptor has been preincubated (desensitized) with elevated concentrations of acetylcholin…