Multiple sclerosis: Benefits of q-space imaging in evaluation of normal-appearing and periplaque white matter

Introduction

Diffusion tensor imaging (DTI) reveals white matter pathology in patients with multiple sclerosis (MS). A recent non-Gaussian diffusion imaging technique, q-space imaging (QSI), may provide several advantages over conventional MRI techniques in regard to in vivo evaluation of the disease process in patients with MS. The purpose of this study is to investigate the use of root mean square displacement (RMSD) derived from QSI data to characterize plaques, periplaque white matter (PWM), and normal-appearing white matter (NAWM) in patients with MS.

Methods

We generated apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps by using conventional DTI data from 21 MS patients; we generated RMSD maps by using QSI data from these patients. We used the Steel–Dwass test to compare the diffusion metrics of regions of interest in plaques, PWM, and NAWM.

Results

ADC differed (P < 0.05) between plaques and PWM and between plaques and NAWM. FA differed (P < 0.05) between plaques and NAWM. RMSD differed (P < 0.05) between plaques and PWM, plaques and NAWM, and PWM and NAWM.

Conclusion

RMSD values from QSI may reflect microstructural changes and white-matter damage in patients with MS with higher sensitivity than do conventional ADC and FA values.     

Unique Structural Properties of 2,4,6‐Tri‐tert‐butylanilide: Isomerization and Switching between Separable Amide Rotamers through the Reaction of Anilide Enolates

Herein, we report a unique structural property of 2,4,6‐tri‐tert‐butylanilide, which can be separated into its amide rotamers at room temperature. Interconversion between the rotamers of anilide enolates occurs readily at room temperature and their reaction with electrophiles gives mixtures of the rotamers in a ratio that depends on the reactivity of the corresponding electrophile. That is, the reaction of the 2,4,6‐tri‐tert‐butylacetanilide enolate with reactive electrophiles, such as allyl bromide or protic acids, gives mixtures of the anilide rotamers in which the E rotamer is the major component, whereas less‐reactive electrophiles, such as 1‐bromopropane and 2‐iodopropane, yield mixtures of the rotamers in which the Z rotamer is the major component. The rotameric ratio of the product is also strongly dependent on the reactivity of the anilide enolate. Switching between the anilide rotamers can be achieved through protonation of a less‐reactive enolate by a less‐reactive protic acid and thermal isomerization of the anilide.     

Efficient Synthesis of a Regioregular Oligothiophene Photovoltaic Dye Molecule,MK‐2, and Related Compounds: A Cooperative Hypervalent Iodine and Metal‐Catalyzed Synthetic Route

We have successfully established an efficient route to the core structure of donor–acceptor head‐to‐tail (H–T)‐linked regioregular oligothiophenes, which includes the following key synthetic steps, that is, hypervalent iodine induced direct and regioselective coupling of thiophenes and the use of the obtained bithiophenes as excellent coupling substrates for the Suzuki and Stille couplings. The versatility of this new approach is highlighted in the dramatic improvement of the yield (ca. 59 % overall yield) of MK‐2, a high‐performance organic dye, for photovoltaic applications.     

Facile synthesis of 3-(aminomethyl)isoquinolines by copper-catalysed domino four-component coupling and cyclisation

Copper(i)-catalysed domino four-component coupling-cyclisation using 2-ethynylbenzaldehydes, paraformaldehyde, secondary amine, and t-BuNH(2) in DMF leads to direct and efficient formation of 3-(aminomethyl)isoquinolines in good to high yields.     

Total synthesis of (+/-)-lysergic acid, lysergol, and isolysergol by palladium-catalyzed domino cyclization of amino allenes bearing a bromoindolyl group

Ergot alkaloids and their synthetic analogs have been reported to exhibit broad biological activity. We investigated direct construction of the C/D ring system of ergot alkaloids based on palladium-catalyzed domino cyclization of amino allenes. With this biscyclization as the key step, total synthesis of (+/-)-lysergic acid, (+/-)-lysergol, and (+/-)-isolysergol was achieved.     

Efficient synthesis of trifluoromethyl and related trisubstituted alkene dipeptide isosteres by palladium-catalyzed carbonylation of amino acid derived allylic carbonates

A novel stereoselective synthetic approach to (Z)-trifluoromethylalkene dipeptide isosteres (CF(3)-ADIs) is described. Starting from readily available N-Boc-L-phenylalanine, Phe-Gly type CF(3)-ADIs were obtained through palladium-catalyzed carbonylation of allylic carbonates under CO. While the reaction of N-Boc derivatives proceeds in excellent yields but lower stereoselectivity (E: Z = 62:38-43:57), the reaction of the N, N-diBoc derivative exclusively affords the desired (Z)-isomer in 61% yield. We also present a highly stereoselective synthesis of several Phe-Gly type trisubstituted alkene dipeptide isosteres by palladium-catalyzed carbonylation.     

Microscopic characterisation of self-assembled colloidal particles in electrohydrodynamic convection of a low-birefringence nematic liquid crystal

Electrokinetics of small particles immersed in anisotropic fluids is attracting attention in recent years. Here we focus on microscopic appearance of single as well as self-assembled particles moving in the electrohydrodynamic convection (EHC) of a nematic liquid crystal with low birefringence. Characterisation of the birefringent properties is made by polarised light microscopy under different illumination conditions. Because of the small optical anisotropy, the director distortion around the particles clearly exhibits distinctive colours on both sides depending on the height in the cell. The observation can be explained as the change in the net phase retardation of the light. It is also found that a caterpillar-like motion is possible by tuning temperature, although the horizontal size of the EHC rolls is relatively narrow.     

Preparation of large crystals of photoactive yellow protein for neutron diffraction and high resolution crystal structure analysis

The exact positions of all the hydrogen atoms in photoactive yellow protein (PYP) is important for understanding the molecular mechanism of the photoreaction because the protonation/deprotonation of certain amino acid residues and rearrangements in the hydrogen bond network are involved in the conformational changes of PYP. Neutron crystallography is one of the most effective methods to determine the hydrogen positions. However, a large crystal is required for neutron crystallography because a neutron-incident flux is quite limited. In addition, the crystal should be grown from heavy water to reduce the incoherent background from hydrogen. We prepared a large crystal of PYP (dimensions: 1.5 x 0.7 x 0.7 mm3) for neutron crystallography using ammonium sulfate with sodium chloride. The obtained large crystal gave X-ray diffraction spots up to 0.84 angstroms. Although some of the hydrogen atoms could be observed in the high resolution X-ray crystal structure, functionally important hydrogen atoms were impossible to see, indicating the importance of neutron crystallography. Thus, we optimized the crystallization conditions with heavy water and successfully obtained neutron diffraction spots up to 2.1 angstroms with the crystal in D2O.     

The first total synthesis and structural determination of YCM1008A

The first total synthesis and structural determination of YCM1008A, a Ca²⁺ signaling inhibitor, have been achieved. The N-methoxy pyrano-pyridone moiety was synthesized by successive O- and N-conjugate additions with diketoamide 15. The absolute structure was determined to be (2R,3R,4S,8′R)-configuration.