Insights into channel function via channel dysfunction

The nicotinic synapse has been a touchstone for advances in neuroscience ever since Jean Nicot, the French ambassador to Portugal, sent some tobacco seeds home to Paris in 1550 with a note that the New World plant had interesting effects when smoked. Now the muscle nicotinic acetylcholine receptor (nAChR) is a well-studied example of ligand-gated ion channels. After a motor neuron is stimulated, the nerve impulse reaches the presynaptic terminal, where it evokes release of acetylcholine (ACh) into the synapse. The nAChR depolarizes the postsynaptic muscle and triggers muscle action potentials; muscle contraction follows. To date, several nAChR subtypes have been successfully isolated, purified, imaged, and expressed, and unitary currents have been recorded from these channels (1). Researchers continue to unravel the molecular mechanisms of these macromolecules that are embedded in membranes at vertebrate nerve-muscle synapses, at invertebrate nicotinic synapses (which explains why nicotine-producing tobacco plants have a select advantage against invertebrate pests), and in the vertebrate central system (which explains Jean Nicot’s fascination with those leaves). However, the precise structural events that trigger channel opening or "gating" remain mostly unknown

Comparison of enzymatic activities of the reactions of linoleic and linolenic acids ruminal biohydrogenation

Introduction: Biohydrogenation (BH) is a microbial hydrogenation of dietary unsaturated fatty acids occurring in the rumen. BH is of interest because it directly affects the fatty acids composition of milk and meat. The linoleic acid (C18:2) BH is divided into three reactions: isomerisation into conjugated linoleic acids (CLA), reduction to trans-C18:1 and then to stearic acid (C18:0); that of alpha-linolenic acid (C18:3) into four reactions: isomerisation to conjugated linolenic acid (CLnA), reduction to trans11,cis15-C18:2, then to trans-C18:1 and finally to C18:0. The aim of this study was to compare enzymatic activities of the reactions of C18:2 BH to those of C18:3 BH. Materials and methods: Rumen fluid was collected from a dry dairy cow and strained on a metal sieve (1,6mm). Then, it was mixed with Chloramphenicol (Cm), an inhibitor of protein synthesis in prokaryotes, at a dose of 1mg/mL . Incubations were prepared by adding 1mL of rumen fluid + Cm, with 1mL of bicarbonate buffer and 1mg of C18:2 or C18:3 (purity ≥ 99%, Sigma), and were conducted in a waterbath at 39°C, with 3h agitation, in 3 replicates. Fatty acids were quantified by gas chromatography. Then rate (v, mg/L/h) and efficiency (E, %) of the reactions were calculated. Results and Discussion: The isomerisation of C18:3 was quicker and more efficient than that of C18:2, which was probably saturated2 (v = 129.6 vs. 94.4 mg/L/h; E = 80.2 vs. 52.7%, respectively. The reductions of conjugated isomers were rapid and efficient, mainly for CLnA (v = 123.7 mg/L/h; E= 95.5%) compared to CLA (v = 78.1 mg/L/h; E= 82.0%). However, for C18:2 BH, cis9,trans11-CLA disappeared quicker than trans10,cis12-CLA so that their respective production after 3h incubation was +0.016mg vs. +0.073mg. The last reduction of C18:2 BH was the slowest (v = 63.8 mg/L/h; E= 68.9%), and constituted the limiting step, resulting in trans-C18:1 accumulation. The second reduction of C18:3 BH was very slow and poorly efficient (v = 48.8 mg/L/h; E= 38.2%), so that trans11,cis15-C18:2 highly accumulated (+0.450mg produced). The last reduction of C18:3 BH was also a slow and poorly efficient reaction (v = 38.8 mg/L/h; E= 41.9%), so that trans-C18:1 would probably have accumulated with a longer incubation. Conclusion: The BH of C18:2 and C18:3 were not exactly similar. C18:2 BH was slower, its isomerisation seemed to be rapidly saturable and the limiting step was the final reduction inducing an accumulation of trans-C18:1. For C18:3 BH, first and second reactions were rapid, so that few CLnA was present in the media. Contrarily, the third and fourth reactions were slow so that trans11,cis15-C18:2 firstly accumulated. Such an evolution was previously reported in vitro with live mixed ruminal bacteria2, indicating that the evaluation of BH does not require live bacteria, and confirming the validity and interest of this enzymatic approach

Value Chain: From iDMU to Shopfloor Documentation of Aeronautical Assemblies

Competition in the aerospace manufacturing companies has led them to continuously improve the efficiency of their processes from the conceptual phase to the start of production and during operation phase, providing services to clients. PLM (Product Lifecycle Management) is an end-to-end business solution which aims to provide an environment of information about the product and related processes available to the whole enterprise throughout the product’s lifecycle. Airbus designs and industrializes aircrafts using Concurrent Engineering methods since decades. The introduction of new PLM methods, procedures and tools, and the need to improve processes efficiency and reduce time-to-market, led Airbus to pursue the Collaborative Engineering method. Processes efficiency is also impacted by the variety of systems existing within Airbus. Interoperability rises as a solution to eliminate inefficiencies due to information exchange and transformations and it also provides a way to discover and reuse existing information. The ARIADNE project (Value chain: from iDMU to shopfloor documentation of aeronautical assemblies) was launched to support the industrialization process of an aerostructure by implementing the industrial Digital Mock-Up (iDMU) concept in a Collaborative Engineering framework. Interoperability becomes an important research workpackage in ARIADNE to exploit and reuse the information contained in the iDMU and to create the shop floor documentation. This paper presents the context, the conceptual approach, the methodology adopted and preliminary results of the project

Transition and control in rotating-disk boundary-layer

voir pd

Expanding The Automobile Search Incident to Arrest: New York v. Belton

This Note will examine the basis for the holding in Belton, consider the changes in existing search incident to arrest law and the effects that it will have on other areas of the law

An Application of Discourse Analysis Methodology in the Exegesis of John 17

This study applies discourse analysis methodology to the study of the seventeenth chapter of John. Instead of adopting the typical three-fold division of Jesus\u27 prayer based upon the three referents (Jesus, the immediate disciples, and future disciples), greater attention is given to Jesus\u27 requests and final commitment, the mainline verbs. By giving more structural significance to the mainline verbs, the structural division and natural outline of Jesus\u27 prayer become more evident

New Series Expansions of the Gauss Hypergeometric Function

The Gauss hypergeometric function ${}_2F_1(a,b,c;z)$ can be computed by using the power series in powers of $z, z/(z-1), 1-z, 1/z, 1/(1-z),(z-1)/z$. With these expansions ${}_2F_1(a,b,c;z)$ is not completely computable for all complex values of $z$. As pointed out in Gil, {\it et al.} [2007, \S2.3], the points $z=e^{\pm i\pi/3}$ are always excluded from the domains of convergence of these expansions. B\"uhring [1987] has given a power series expansion that allows computation at and near these points. But, when $b-a$ is an integer, the coefficients of that expansion become indeterminate and its computation requires a nontrivial limiting process. Moreover, the convergence becomes slower and slower in that case. In this paper we obtain new expansions of the Gauss hypergeometric function in terms of rational functions of $z$ for which the points $z=e^{\pm i\pi/3}$ are well inside their domains of convergence . In addition, these expansion are well defined when $b-a$ is an integer and no limits are needed in that case. Numerical computations show that these expansions converge faster than B\"uhring's expansion for $z$ in the neighborhood of the points $e^{\pm i\pi/3}$, especially when $b-a$ is close to an integer number.Comment: 18 pages, 6 figures, 4 tables. In Advances in Computational Mathematics, 2012 Second version with corrected typos in equations (18) and (19