Synthesis of 6-deoxy-5-thio-d-glucose

Three routes were investigated for the conversion of d-glucose into the title compound. In the first approach, reduction of the 5,6-thürane ring of 5,6-dideoxy-5,6-epithio-1,2-O-isopropylidene α-d-glucofuranose (17) as well as that of its 3-O-allyl derivative (13) with lithium aluminium hydride was investigated; 17 afforded the corresponding 6-deoxy derivative besides di-, tri-, and poly-mers, whereas only polymers were formed from 13. In the second approach, the oxirane ring of was reduced by sodium borohydride and the resulting 6-deoxy derivative was converted into the 5-thiobenzoate; the corresponding hex-4-enofuranose was formed as a byproduct. In the third approach partial mesylation of methyl 5-thio-α-d-glucopyranoside was attempted, but the 6-mesylate 27 could be isolated only in modest yield (28%) together with rearranged 2,5-thioanhydromannofuranoside derivatives. The mechanism of this rearrangement is discussed in detail. The 6-mesylate 27 was converted via the 6-iodo derivative into the title compound.     

Conformation of 4-thio-l-lyxono-1,4-lactone in solution and in the crystalline state

The conformation in ²H₂O of 4-thio-l-lyxono-1,4-lactone (1) was studied by nuclear magnetic resonance spectroscopy, by means of homonuclear (J_1H,1H) and heteronuclear (J_1H,13C) coupling constants. The couplings were directly measured by a two-dimensional heteronucleus-coupled ω₁ hetero-half-filtered proton-proton correlation (HETLOC) experiment, which does not require ¹³C isotopic enrichment. In solution, the thiolactone ring of 1 adopts preferentially the E₃ conformation, and its hydroxymethyl group populates mainly the gt rotamer. The X-ray diffraction data of a single crystal of 1 indicates that also in the solid state the thiolactone ring adopts an E₃ conformation, with a puckering somewhat larger than that observed for aldono-1,4-lactones and furanose rings. The molecules are linked by hydrogen bonds, which form chains. Particularly, O-5 is fully engaged as donor and acceptor in hydrogen bonding and the rotameric conformation of the hydroxymethyl group of 1 is fixed in the tg form.     

Role of local nonspiking interneurons in the generation of rhythmic motor activity in the stick insect

Local nonspiking interneurons in the thoracic ganglia of insects are important premotor elements in posture control and locomotion. It was investigated whether these interneurons are involved in the central neuronal circuits generating the oscillatory motor output of the leg muscle system during rhythmic motor activity. Intracellular recordings from premotor nonspiking interneurons were made in the isolated and completely deafferented mesothoracic ganglion of the stick insect in preparations exhibiting rhythmic motor activity induced by the muscarinic agonist pilocarpine. All interneurons investigated provided synaptic drive to one or more motoneuron pools supplying the three proximal leg joints, that is, the thoraco-coxal joint, the coxa-trochanteral joint and the femur-tibia joint. During rhythmicity in 83% (n=67) of the recorded interneurons, three different kinds of synaptic oscillations in membrane potential were observed: (1) Oscillations were closely correlated with the activity of motoneuron pools affected; (2) membrane potential oscillations reflected only certain aspects of motoneuronal rhythmicity; and (3) membrane potential oscillations were correlated mainly with the occurrence of spontaneous recurrent patterns (SRP) of activity in the motoneuron pools. In individual interneurons membrane potential oscillations were associated with phase-dependent changes in the neuron's membrane conductance. Artificial changes in the interneurons' membrane potential strongly influenced motor activity. Injecting current pulses into individual interneurons caused a reset of rhythmicity in motoneurons. Furthermore, current injection into interneurons influenced shape and probability of occurrence for SRPs. Among others, identified nonspiking interneurons that are involved in posture control of leg joints were found to exhibit the above properties. From these results, the following conclusions on the role of nonspiking interneurons in the generation of rhythmic motor activity, and thus potentially also during locomotion, emerge: (1) During rhythmic motor activity most nonspiking interneurons receive strong synaptic drive from central rhythm-generating networks; and (2) individual nonspiking interneurons some of which underlie sensory-motor pathways in posture control, are elements of central neuronal networks that generate alternating activity in antagonistic leg motoneuron pools. © 1995 John Wiley & Sons, Inc.     

Na_2SO_3和NaHCO_3对叶绿体CF_1－ATPase活力作用的机制

Ｎａ２ＳＯ３对热－ＤＴＴ活化的游离ＣＦ１及类囊体膜上ＣＦ１－ＡＴＰａｓｅ活力均有显著的促进作用,ＮａＨＣＯ３亦有明显的促进作用。Ｎａ２ＳＯ３和ＮａＨＣＯ３的促进作用与它们解除Ｍｇ２＋的抑制作用有关。从ＮａＨＣＯ３和Ｎａ２ＳＯ３及它们与Ｍｇ２＋之间的竞争性关系,表明三者是结合在酶的同一部位上。Ｎａ２ＳＯ３可明显降低热－ＤＴＴ活化的游禹ＣＦ１－ＡＴＰａｓｅ催化反应的活化能,这可能与促进产物ＡＤＰ的释放有关。     

Abstractions can be causes — A response to professor hogan

In Can Abstractions be Causes, David Johnson defends the view that abstractions can have causal force. He offers as his own example of natural kinds ecological niches, arguing that the causal force of these niches in nature is akin to the force of Aristotelian final causes. He concludes that, rooted as it is in seventeenth century mechanism, the currently-accepted model of causality which recognises only efficient causes is inadequate to the needs of contemporary science. In Natural Kinds and Ecological Niches — Response to Johnson's Paper, Melinda Hogan offers a critique of Johnson's paper which, by begging the question in favor of the very sort of causality Johnson seeks to supplement, misses the epistemological implications of his idea. In this paper I will attempt to clarify and defend Johnson's position, pointing out some of its implications for the epistemology of science in general.     

Metabolic compartmentation and substrate channelling in muscle cells

The published experimental data and existing concepts of cellular regulation of respiration are analyzed. Conventional, simplified considerations of regulatory mechanism by cytoplasmic ADP according to Michaelis-Menten kinetics or by derived parameters such as phosphate potential etc. do not explain relationships between oxygen consumption, workload and metabolic state of the cell. On the other hand, there are abundant data in literature showing microheterogeneity of cytoplasmic space in muscle cells, in particular with respect to ATP (and ADP) due to the structural organization of cell interior, existence of multienzyme complexes and structured water phase. Also very recent experimental data show that the intracellular diffusion of ADP is retarded in cardiomyocytes because of very low permeability of the mitochondrial outer membrane for adenine nucleotidesin vivo. Most probably, permeability of the outer mitochondrial membrane porin channels is controlled in the cellsin vivo by some intracellular factors which may be connected to cytoskeleton and lost during mitochondrial isolation. All these numerous data show convincingly that cellular metabolism cannot be understood if cell interior is considered as homogenous solution, and it is necessary to use the theories of organized metabolic systems and substrate-product channelling in multienzyme systems to understand metabolic regulation of respiration. One of these systems is the creatine kinase system, which channels high energy phosphates from mitochondria to sites of energy utilization. It is proposed that in muscle cells feed-back signal between contraction and mitochondrial respiration may be conducted by metabolic wave (propagation of oscillations of local concentration of ADP and creatine) through cytoplasmic equilibrium creatine and adenylate kinases and is amplified by coupled creatine kinase reaction in mitochondria. Mitochondrial creatine kinase has experimentally been shown to be a powerful amplifier of regulatory action of weak ADP fluxes due to its coupling to adenine nucleotide translocase. This phenomenon is also carefully analyzed.It is easier to explain biochemistry in terms of transport than it is to explain transport in terms of biochemistry. P. Mitchell The Ninth Sir Hans Krebs Lecture, Dresden, July 2, 1978.     

Oscillations in the electrical resistance of Nitellopsis obtusa nodes

Oscillatory changes of the electrical resistance across the nodal complex of Nitellopsis obtusa (Desv. in Lois) J. Gr. were observed in experiments performed for 40–150 min with the use of external electrodes and microelectrodes. Three main patterns of node resistance oscillations were similar to those found for membrane potential and resistance. The presented findings indicate an oscillatory behaviour of the plasmodesmata system at the node, which may be connected with e.g. pulsatile variations in the number of open plasmodesmata.     

Mutational and crystallographic analyses of the active site residues of the Bacillus circulans xylanase.

Using site-directed mutagenesis we have investigated the catalytic residues in a xylanase from Bacillus circulans. Analysis of the mutants E78D and E172D indicated that mutations in these conserved residues do not grossly alter the structure of the enzyme and that these residues participate in the catalytic mechanism. We have now determined the crystal structure of an enzyme-substrate complex to 108 A resolution using a catalytically incompetent mutant (E172C). In addition to the catalytic residues, Glu 78 and Glu 172, we have identified 2 tyrosine residues, Tyr 69 and Tyr 80, which likely function in substrate binding, and an arginine residue, Arg 112, which plays an important role in the active site of this enzyme. On the basis of our work we would propose that Glu 78 is the nucleophile and that Glu 172 is the acid-base catalyst in the reaction.