Therapeutic target metabolism observed using hyperpolarized 15N choline

Choline is a precursor of cellular phospholipid metabolism that provides Magnetic Resonance (MR) and Positron Emission Tomography (PET) biomarkers for cancer detection and response assessment. Employing Dynamic Nuclear Polarization we show that the MR signal of 15N in choline can be enhanced by at least 4 orders of magnitude with a relaxation time of ca. 4 min, providing a method to observe the action of choline kinase, an important target for novel cancer therapeutics.     

有机硅活性中间体的研究 II. 一些含环丙基的有机硅化合物的合成及其结构

用锂有机物的方法合成了四种含有环丙基有机硅化合物,对上述每种化合物中可能存在着的立体异构进行了分离和和构型测定。     

Highly selective excitation in biomolecular NMR by frequency-switched single-transition cross-polarization

A new method for selective excitation in biomolecular NMR uses two-fold single-transition cross-polarization between protons and nitrogen-15 or carbon-13 nuclei. Switching the frequencies between the forward and backward transfer steps allows one to select a multiplet pattern that is associated with a single pair of spins in a medium-size protein. The efficiency of the transfer benefits from so-called TROSY line-narrowing effects which arise from interference between relaxation mechanisms.     

Conformational exchange in pimonidazole--a hypoxia marker

Pimonidazole is one of a series of nitroimidazole compounds that is widely used as a marker for qualitative and quantitative assessment of tumour hypoxia. We have observed a novel dynamic conformational exchange process in this molecule in aqueous solution. By a combination of 1H, 13C, two-dimensional 1H-1H EXchange SpectroscopY (EXSY) and spectral simulation, we unambiguously attribute the conformational exchange process to flipping of the six-membered heterocyclic ring.     

Selective homonuclear Hartmann–Hahn for 13C→13C polarization transfer in solution state NMR

Polarization transfer has become a commonplace technique for the enhancement of a variety of nuclei in high field nuclear magnetic resonance (NMR). In this paper the homonuclear Hartmann-Hahn method for polarization transfer is revisited and it is shown that a 90% transfer of polarization can be achieved experimentally between a pair of scalar coupled ¹³C nuclei in a sample of isotopically enriched glycine. This may show particular utility in the field of dynamic nuclear polarization (DNP) and could be used as an addendum to already established DNP techniques allowing the favourable enhancement to be ‘stored’ on long-lived nuclei and subsequently transferred to shorter-lived nuclei prior to observation.     

Offset Profiles of Selective Pulses in Isotopically Labeled Macromolecules

The experimental verification of offset profiles and calibration of selective pulses in NMR is usually carried out with doped water samples but not under conditions typical of macromolecules with shortT₂, longT₁, and possibly homo- and heteronuclear couplings. A new method for selective excitation in isotopically labeled macromolecules is shown to be particularly suited to this purpose. This is illustrated for a backbone amide resonance in a sample of¹⁵N-labeled human ubiquitin.     

The microwave heating of two-dimensional slabs with small Arrhenius absorptivity

The microwave heating of two-dimensional slabs in a long rectangularwaveguide propagating the TE₁₀ mode is examined. The temperaturedependency of the electrical conductivity and the thermal absorptivityis assumed to be governed by the Arrhenius law, while both theelectrical permittivity and the magnetic permeability are assumedconstant. The governing equations are the forced heat equationand the steady-state version of Maxwell's equation while theboundary conditions take into account both convective and radiativeheat loss. Approximate analytical solutions, valid for smallthermal absorptivity, are found for the temperature and theelectric-field amplitude using the Galerkin method. As the Arrheniuslaw is not amenable analytically, it is approximated by a rational-cubicfunction. At the steady state the temperature versus power relationshipis found to be multivalued; at the critical power level thermalrunaway occurs when the temperature jumps from the lower (cool)temperature branch to the upper (hot) temperature branch ofthe solution. In the steady-state limit the approximate analyticalsolutions are compared with the numerical solutions of the governingequations for various special cases. These are the limits ofsmall and large heat loss and an intermediate case involvingradiative heat loss. Results are also presented for a case wheredifferential cooling occurs on the different sides on the slab.An alternative heating scenario, where one end of the waveguideis blocked by a short, is also considered. The approximate solutionsare found for this geometry and compared in the small Biot-numberlimit to Kriegsmann (1997). Also, a control process is presented,which allows thermal runaway to be avoided and the desired finalsteady state to be reached. Various special cases of the feedbackparameters associated with the control process are examined.     

Bi-directional modulation of AMPA receptor unitary conductance by synaptic activity

Background  

Knowledge of how synapses alter their efficiency of communication is central to the understanding of learning and memory. The most extensively studied forms of synaptic plasticity are long-term potentiation (LTP) and its counterpart long-term depression (LTD) of AMPA receptor-mediated synaptic transmission. In the CA1 region of the hippocampus, it has been shown that LTP often involves a rapid increase in the unitary conductance of AMPA receptor channels. However, LTP can also occur in the absence of any alteration in AMPA receptor unitary conductance. In the present study we have used whole-cell dendritic recording, failures analysis and non-stationary fluctuation analysis to investigate the mechanism of depotentiation of LTP.     

Twisting DNA: single molecule studies

Over the past 10 years a number of new techniques have emerged that allow the manipulation of single DNA molecules and other biopolymers (RNA, proteins, etc.). These experiments have permitted the measurement of the DNA stretching and twisting elasticity and have consequently revealed the essential role played by the DNA mechanical properties in its interactions with proteins. We shall first describe the different methods used to stretch and twist single DNA molecules. We will then focus on its behaviour under torsion, especially by discussing the different methods used to estimate its torsional modulus.     

Identification of Spin Diffusion Pathways in Isotopically Labeled Biomolecules

One-dimensional NOE experiments applicable to labeled macromolecules are presented which allow the manipulation of specific spin diffusion pathways and thus unambiguously identify clandestine spins through which the direct NOE is mediated. A treatment of spin diffusion using average Liouvillian theory is shown to describe adequately these phenomena. Experiments are carried out on an 15N-labeled sample of human ubiquitin.