A GC/MS-based metabolomic approach for diagnosing citrin deficiency

Citrin is the hepatic mitochondrial aspartate–glutamate carrier that is encoded by the gene SLC25A13. Citrin deficiency often leads to hyperammonemia, for which the current treatment concept is different from that for primary hyperammonemias. Metabolite level diagnosis, often referred to as chemical diagnosis, is not always successful in identifying citrin deficiency immediately or in a timely fashion. We previously made the chemical diagnosis of citrin deficiency in ten patients from nine families. In order to devise a more rapid and more accurate chemical diagnosis of this disorder than is currently available, we reinvestigated the gas chromatography/mass spectrometry-based urine metabolome in these patients. In patients aged 2 to 5 months, prominent biomarkers detected included one or more of the following metabolites: tyrosine, p-hydroxyphenyllactate, p-hydroxyphenylpyruvate, and N-acetyltyrosine, galactose, galactitol and galactonate, glucose, glucitol, and cystathionine. These biomarkers are less prominent in older patients, but are not increased in argininosuccinate synthetase deficiency or other hyperammonemias. α-Ketoglutaramate (KGM), a recently recognized urinary biomarker of primary hyperammonemias associated with defects of the urea cycle, was increased in most patients with citrin deficiency studied here in spite of normal urinary levels of glutamine (the immediate precursor of KGM), 5-oxoproline, glutamate, aspartate, and asparagine. Other important urinary biomarkers that should be measured for differential diagnosis of hyperammonemias, including orotate, uracil, and β-ureidopropionate, were not increased. The presence of citrulline and citrulline-derived metabolites was noted in all cases. The present study shows that noninvasive urine metabolomics, together with an analysis of selected metabolites or groups of metabolites, provides a more reliable and rapid chemical diagnosis of citrin deficiency than was previously available and more readily differentiates this disorder from other hyperammonemic syndromes.     

Experimental demonstration of the induction synchrotron

We report an experimental demonstration of the induction synchrotron, the concept of which has been proposed as a future accelerator for the second generation of neutrino factory or hadron collider. The induction synchrotron supports a superbunch and a superbunch permits more charge to be accelerated while observing the constraints of the transverse space-charge limit. By using a newly developed induction acceleration system instead of radio-wave acceleration devices, a single proton bunch injected from the 500 MeV booster ring and captured by the barrier bucket created by the induction step voltages was accelerated to 6 GeV in the KEK proton synchrotron.     

Molecular clusters in two-dimensional surface-confined nanoporous molecular networks: structure, rigidity, and dynamics

The self-assembly of a series of hexadehydrotribenzo[12]annulene (DBA) derivatives has been investigated by scanning tunneling microscopy (STM) at the liquid/solid interface in the absence and presence of nanographene guests. In the absence of appropriate guest molecules, DBA derivatives with short alkoxy chains form two-dimensional (2D) porous honeycomb type patterns, whereas those with long alkoxy chains form predominantly dense-packed linear type patterns. Added nanographene molecules adsorb in the pores of the existing 2D porous honeycomb type patterns or, more interestingly, they even convert the guest-free dense-packed linear-type patterns into guest-containing 2D porous honeycomb type patterns. For the DBA derivative with the longest alkoxy chains (OC20H41), the pore size, which depends on the length of the alkoxy chains, reaches 5.4 nm. Up to a maximum of six nanographene molecules can be hosted in the same cavity for the DBA derivative with the OC20H41 chains. The host matrix changes its structure in order to accommodate the adsorption of the guest clusters. This flexibility arises from the weak intermolecular interactions between interdigitating alkoxy chains holding the honeycomb structure together. Diverse dynamic processes have been observed at the level of the host matrix and the coadsorbed guest molecules.     

Synthesis of a calix[4]crown modified with germanium‐containing side chains

A germacalix‐crown, 25,27‐bis[1‐(3‐trimethylgermylpropyl)oxy]calix[4]arene‐crown‐6, 1,3‐alternate ( 1a ), and its carbon analog, 25,27‐bis‐[1‐(4,4‐dimethylpentyl)oxy]calix[4]arene‐crown‐6, 1,3‐alternate ( 1b ), were prepared and their structures were confirmed by elemental analysis and ¹H and ¹³C NMR spectroscopy. A cation transport test indicated that both compounds exhibited much the same cation transport ability, so that the role of the germanium moiety in capturing and transporting counteranions is not yet clear. Copyright © 2005 John Wiley & Sons, Ltd.     

The site distribution of Ti and V and the metal-metal interaction in the ternary system (V,Ti)5S8

The phase relations of the ternary system V_1?xTi_xS_1.57 are presented on the basis of X-ray diffractometry. The site distribution of Ti and V atoms in the structure is clarified through an NMR absorption study at room temperature. The phase relations and the site distribution of Ti and V, which appear to be closely related to each other, are discussed in terms of the metal-metal interaction of the face-shared octahedra in the metal-deficient distorted NiAs structure.     

Catalytic Ni/Cr-mediated macrocyclization without use of high-dilution techniques

The feasibility of catalytic Ni/Cr-mediated macrocyclization was demonstrated for the two substrates chosen from the halichondrin area. With 5 mol % of Ni and Cr catalysts, the macrocyclization was realized without use of high-dilution techniques. The reported method has a number of appealing features, including user-friendliness, easy workup, apparent scalability, and cost-effectiveness. In addition, all the required reagents are commercially available or obtainable in one or two steps from commercially available chemicals.