Computed tomography findings in liver fibrosis and cirrhosis

Abstract PRINCIPLES: Computed tomography (CT) is inferior to the fibroscan and laboratory testing in the noninvasive diagnosis of liver fibrosis. On the other hand, CT is a frequently used diagnostic tool in modern medicine. The auxiliary finding of clinically occult liver fibrosis in CT scans could result in an earlier diagnosis. The aim of this study was to analyse quantifiable direct signs of liver remodelling in CT scans to depict liver fibrosis in a precirrhotic stage. METHODS: Retrospective review of 148 abdominal CT scans (80 liver cirrhosis, 35 precirrhotic fibrosis and 33 control patients). Fibrosis and cirrhosis were histologically proven. The diameters of the three main hepatic veins were measured 1-2 cm before their aperture into the inferior caval vein. The width of the caudate and the right hepatic lobe were divided, and measured horizontally at the level of the first bifurcation of the right portal vein in axial planes (caudate-right-lobe ratio). A combination of both (sum of liver vein diameters divided by the caudate-right lobe ratio) was defined as the ld/crl ratio. These metrics were analysed for the detection of liver fibrosis and cirrhosis. RESULTS: An ld/crl-r <24 showed a sensitivity of 83% and a specificity of 76% for precirrhotic liver fibrosis. Liver cirrhosis could be detected with a sensitivity of 88% and a specificity of 82% if ld/crl-r <20. CONCLUSION: An ld/crl-r <24 justifies laboratory testing and a fibroscan. This could bring forward the diagnosis and patients would profit from early treatment in a potentially reversible stage of disease.

Trypanosoma brucei RRM1 is a nuclear RNA-binding protein and modulator of chromatin structure

TbRRM1 of Trypanosoma brucei is a nucleoprotein that was previously identified in a search for splicing factors in T. brucei. We show that TbRRM1 associates with mRNAs and with the auxiliary splicing factor polypyrimidine tract-binding protein 2, but not with components of the core spliceosome. TbRRM1 also interacts with several retrotransposon hot spot (RHS) proteins and histones. RNA immunoprecipitation of a tagged form of TbRRM1 from procyclic (insect) form trypanosomes identified ca. 1,500 transcripts that were enriched and 3,000 transcripts that were underrepresented compared to cellular mRNA. Enriched transcripts encoded RNA-binding proteins, including TbRRM1 itself, several RHS transcripts, mRNAs with long coding regions, and a high proportion of stage-regulated mRNAs that are more highly expressed in bloodstream forms. Transcripts encoding ribosomal proteins, other factors involved in translation, and procyclic-specific transcripts were underrepresented. Knockdown of TbRRM1 by RNA interference caused widespread changes in mRNA abundance, but these changes did not correlate with the binding of the protein to transcripts, and most splice sites were unchanged, negating a general role for TbRRM1 in splice site selection. When changes in mRNA abundance were mapped across the genome, regions with many downregulated mRNAs were identified. Two regions were analyzed by chromatin immunoprecipitation, both of which exhibited increases in nucleosome occupancy upon TbRRM1 depletion. In addition, subjecting cells to heat shock resulted in translocation of TbRRM1 to the cytoplasm and compaction of chromatin, consistent with a second role for TbRRM1 in modulating chromatin structure. IMPORTANCE: Trypanosoma brucei, the parasite that causes human sleeping sickness, is transmitted by tsetse flies. The parasite progresses through different life cycle stages in its two hosts, altering its pattern of gene expression in the process. In trypanosomes, protein-coding genes are organized as polycistronic units that are processed into monocistronic mRNAs. Since genes in the same unit can be regulated independently of each other, it is believed that gene regulation is essentially posttranscriptional. In this study, we investigated the role of a nuclear RNA-binding protein, TbRRM1, in the insect stage of the parasite. We found that TbRRM1 binds nuclear mRNAs and also affects chromatin status. Reduction of nuclear TbRRM1 by RNA interference or heat shock resulted in chromatin compaction. We propose that TbRRM1 regulates RNA polymerase II-driven gene expression both cotranscriptionally, by facilitating transcription and efficient splicing, and posttranscriptionally, via its interaction with nuclear mRNAs.

The U7 snRNP and the hairpin binding protein: Key players in histone mRNA metabolism.

Animal replication-dependent histone mRNAs are subject to several post-transcriptional regulatory processes. Their non-polyadenylated 3' ends are formed preferentially during S phase by a unique nuclear cleavage event. This requires the base pairing between U7 snRNA and a histone spacer element 3' of the cleavage site. Cleavage occurs preferentially after adenosine, at a fixed distance from the hybrid region. A conserved RNA hairpin just upstream of the cleavage site is recognised by the hairpin binding protein (HBP) that acts as an auxiliary processing factor, stabilising the interaction of the histone pre-mRNA with the U7 snRNP. The interaction between HBP and the RNA hairpin is very stable and HBP is also found associated with histone mRNAs on polysomes. The hairpin and presumably, HBP are also required for nuclear export and translation of histone mRNA. Furthermore, histone mRNAs are selectively destabilised in the G2 phase or upon inhibition of DNA synthesis and this regulation is also associated with the hairpin. Recently, HBP-encoding cDNAs were isolated from various organisms. Human, mouse and Xenopus laevis HBPs are similar, while the Caenorhabditis elegans protein has significant homology to the others only in a central RNA binding domain.Copyright 1997 Academic Press Limited

Synthesis and Structural Elucidation of Triazolylmolybdenum(VI) Oxide Hybrids and Their Behavior as Oxidation Catalysts

A large family of bifunctional 1,2,4-triazole molecular tectons (tr) has been explored for engineering molybdenum(VI) oxide hybrid solids. Specifically, tr ligands bearing auxiliary basic or acidic groups were of the type amine, pyrazole, 1H-tetrazole, and 1,2,4-triazole. The organically templated molybdenum(VI) oxide solids with the general compositions [MoO3(tr)], [Mo2O6(tr)], and [Mo2O6(tr)(H2O)2] were prepared under mild hydrothermal conditions or by refluxing in water. Their crystal structures consist of zigzag chains, ribbons, or helixes of alternating cis-{MoO4N2} or {MoO5N} polyhedra stapled by short [N–N]-tr bridges that for bitriazole ligands convert the motifs into 2D or 3D frameworks. The high thermal (235–350 °C) and chemical stability observed for the materials makes them promising for catalytic applications. The molybdenum(VI) oxide hybrids were successfully explored as versatile oxidation catalysts with tert-butyl hydroperoxide (TBHP) or aqueous H2O2 as an oxygen source, at 70 °C. Catalytic performances were influenced by the different acidic–basic properties and steric hindrances of coordinating organic ligands as well as the structural dimensionality of the hybrid.

Clitics, affixes, and wordhood in Garifuna (Arawak): A multidimensional continuum of morphosyntactic boundness

Recent research on wordhood and morphosyntactic boundness suggests that the domains word and clitic do not lend themselves to cross-linguistic categorization but must be defined language specifically. In most languages, it is necessary to define word on two separate levels, the phonological word (p-word) and the grammatical word (g-word), and to describe mismatches between the two. This paper defines those domains for Garifuna, an Arawak language spoken in Honduras, Central America. Garifuna has auxiliary and classifier constructions which make up two p-words, and only one g-word. P-words made up of more than one g-word involve second position enclitics, word scope clitics, and proclitic connectives and prepositions. Garifuna clitics are typically unstressed, able to attach to hosts of any word class and able to string together into clusters. Enclitics are used to express tense-aspect, modality, and adverbial meanings, among others. In other languages, clitic clusters tend to display a fixed order; Garifuna clitic order seems quite free, although certain orders are preferred. Also, contrary to cross-linguistic tendencies, proclitic connectives can act as hosts for enclitic clusters, contradicting the commonly used definition of clitics as phonologically weak elements that need to attach to a host to form a p-word; such clitic-only p-words are problematic for traditional definitions of clitics.

Higher order parametric excitation modes for spaceborne quadrupole mass spectrometers

This paper describes a technique to significantly improve upon the mass peak shape and mass resolution of spaceborne quadrupolemass spectrometers (QMSs) through higher order auxiliary excitation of the quadrupole field. Using a novel multiresonant tank circuit, additional frequency components can be used to drive modulating voltages on the quadrupole rods in a practical manner, suitable for both improved commercial applications and spaceflight instruments. Auxiliary excitation at frequencies near twice that of the fundamental quadrupole RF frequency provides the advantages of previously studied parametric excitation techniques, but with the added benefit of increased sensed excitation amplitude dynamic range and the ability to operate voltage scan lines through the center of upper stability islands. Using a field programmable gate array, the amplitudes and frequencies of all QMS signals are digitally generated and managed, providing a robust and stable voltage control system. These techniques are experimentally verified through an interface with a commercial Pfeiffer QMG422 quadrupole rod system. When operating through the center of a stability island formed from higher order auxiliary excitation, approximately 50% and 400% improvements in 1% mass resolution and peak stability were measured, respectively, when compared with traditional QMS operation. Although tested with a circular rod system, the presented techniques have the potential to improve the performance of both circular and hyperbolic rod geometry QMS sensors.

Enabling the Next Generation of Spaceborne Quadrupole Mass Spectrometers

The quadrupole mass spectrometer (QMS) has over 30 years of spaceflight heritage in making important neutral gas and low energy ion observations. Given their geometrical constraints, these instruments are currently operated at the extreme limit of their capabilities. However, a technique called higher order auxiliary excitation provides a set of novel, robust, electronics-based solutions for improving the performance of these sensors. By driving the quadrupole rods with an additional frequency nearly twice that of the normal RF operating frequency, substantially increased abundance sensitivity, maximum attainable mass resolution, and peak stability can be achieved through operation of voltage scan lines through the center of formed upper stability islands. Such improvements are modeled using numerical simulations of ion trajectories in a quadrupole field with and without applied higher order auxiliary excitation. When compared to a traditional QMS with a mass range up to 500Da, sensors can be designed with the same precision electronics to have expected mass ranges beyond 1500Da with a power increase of less than twice that of its heritage implementations.