Assessment of therapeutic benefit of antiviral therapy in chronic hepatitis C: is hepatic venous pressure gradient a better end point?

Chronic hepatitis C is a major healthcare problem. The response to antiviral therapy for patients with chronic hepatitis C has previously been defined biochemically and by PCR. However, changes in the hepatic venous pressure gradient (HVPG) may be considered as an adjunctive end point for the therapeutic evaluation of antiviral therapy in chronic hepatitis C. It is a validated technique which is safe, well tolerated, well established, and reproducible. Serial HVPG measurements may be the best way to evaluate response to therapy in chronic hepatitis C.

Hereditary hepatic and systemic amyloidosis caused by a new deletion/insertion mutation in the apolipoprotein AI gene.

We report a Spanish family with autosomal-dominant non-neuropathic hereditary amyloidosis with a unique hepatic presentation and death from liver failure, usually by the sixth decade. The disease is caused by a previously unreported deletion/insertion mutation in exon 4 of the apolipoprotein AI (apoAI) gene encoding loss of residues 60-71 of normal mature apoAI and insertion at that position of two new residues, ValThr. Affected individuals are heterozygous for this mutation and have both normal apoAI and variant molecules bearing one extra positive charge, as predicted from the DNA sequence. The amyloid fibrils are composed exclusively of NH2-terminal fragments of the variant, ending mainly at positions corresponding to residues 83 and 92 in the mature wild-type sequence. Amyloid fibrils derived from the other three known amyloidogenic apoAI variants are also composed of similar NH2-terminal fragments. All known amyloidogenic apoAI variants carry one extra positive charge in this region, suggesting that it may be responsible for their enhanced amyloidogenicity. In addition to causing a new phenotype, this is the first deletion mutation to be described in association with hereditary amyloidosis and it significantly extends the value of the apoAI model for investigation of molecular mechanisms of amyloid fibrillogenesis.

Formation and distribution of point defects on a disclination line near a free nematic interface

Point defects of opposite signs can alternately nucleate on the -1/2 disclination line that forms near the free surface of a confined nematic liquid crystal. We show the existence of metastable configurations consisting of periodic repetitions of such defects. These configurations are characterized by a minimal interdefect spacing that is seen to depend on sample thickness and on an applied electric field. The time evolution of the defect distribution suggests that the defects attract at small distances and repel at large distances.

Volcanic stratigraphy of Hannah Point, Livingston Island, South Shetland Islands, Antarctica

The Upper Cretaceous volcanic succession of Hannah Point is the best exposure of the Antarctic Peninsula Volcanic Group on L ivingston Island. The aim of the present paper is to contribute to the characterisation of the stratigr a p hy and petrogr a p hy of this little studied succession, and briefly discuss some aspects of the eru p t ive style of its volcanism. The succession is about 470 m thick and is here subdivided into five lithostratigraphic units (A to E from base to top). Unit A, approximately 120 m thick, is mainly composed of polymict clast-supported volcaniclastic breccias and also includes a dacitic lava laye r. Interstratified in the breccias of this unit, there is a thin laminated devitrified layer which shows some degree of welding. Unit B, approx imately 70 m thick, is almost entirely composed of volcaniclastic breccias, and includes a volcaniclastic conglomerate laye r. Breccias in this unit can be subdivided into two distinct types; polymict clast-supported breccias, and monomict matrix-supported breccias rich in juvenile components and displaying incipient welding. Unit C, about 65 m thick, is mainly composed of basaltic lavas, which are interlayered with minor vo lcaniclastic breccias. Unit D, approximately 65 m thick, is lithologically similar to unit B, composed of an alternation of polymict clasts upported breccias and matrix-supported breccias, and includes a volcaniclastic conglomerate laye r. Unit E, about 150 m thick, is mainly formed of thick andesitic lava layers. Minor basaltic dykes and a few normal faults cut the succession, and the contact betwe e n units A and B can be interpreted both as an unconformity or a fault. The matrix-supported breccias included in the succession of Hannah Point have high contents of juvenile components and incipient welding, which suggest that part of the succession is the result of pyroclastic fragmentation and emplacement from pyroclastic flows. In contrast, the polymict clast-supported breccias suggest reworking of previous deposits and deposition from cool mass flows. The lavas indicate eff u s ive volcanic eruptions, and the absence of features indicative of subaqueous volcanism suggests that at least these portions of the succession were emplaced in a subaerial environment .

Mutation patterns of amino acid tandem repeats in the human proteome

Background: Amino acid tandem repeats are found in nearly one-fifth of human proteins. Abnormal expansion of these regions is associated with several human disorders. To gain further insight into the mutational mechanisms that operate in this type of sequence, we have analyzed a large number of mutation variants derived from human expressed sequence tags (ESTs).Results: We identified 137 polymorphic variants in 115 different amino acid tandem repeats. Of these, 77 contained amino acid substitutions and 60 contained gaps (expansions or contractions of the repeat unit). The analysis showed that at least about 21% of the repeats might be polymorphic in humans. We compared the mutations found in different types of amino acid repeats and in adjacent regions. Overall, repeats showed a five-fold increase in the number of gap mutations compared to adjacent regions, reflecting the action of slippage within the repetitive structures. Gap and substitution mutations were very differently distributed between different amino acid repeat types. Among repeats containing gap variants we identified several disease and candidate disease genes.Conclusion: This is the first report at a genome-wide scale of the types of mutations occurring in the amino acid repeat component of the human proteome. We show that the mutational dynamics of different amino acid repeat types are very diverse. We provide a list of loci with highly variable repeat structures, some of which may be potentially involved in disease.