Meta-analysis of the literature on diagnostic accuracy of SPECT in parkinsonian syndromes

Background  

Parkinson's disease (PD) is the second most common neurodegenerative disorder. One of the most widely used techniques to diagnose PD is a Single Photon Emission Computer Tomography (SPECT) scan to visualise the integrity of the dopaminergic pathways in the brain. Despite this there remains some discussion on the value of SPECT in the differential diagnosis of PD. We did a meta-analysis of all the existing literature on the diagnostic accuracy of both pre- and post-synaptic SPECT imaging in the differential diagnosis of PD.     

ALF--a simulation framework for genome evolution

In computational evolutionary biology, verification and benchmarking is a challenging task because the evolutionary history of studied biological entities is usually not known. Computer programs for simulating sequence evolution in silico have shown to be viable test beds for the verification of newly developed methods and to compare different algorithms. However, current simulation packages tend to focus either on gene-level aspects of genome evolution such as character substitutions and insertions and deletions (indels) or on genome-level aspects such as genome rearrangement and speciation events. Here, we introduce Artificial Life Framework (ALF), which aims at simulating the entire range of evolutionary forces that act on genomes: nucleotide, codon, or amino acid substitution (under simple or mixture models), indels, GC-content amelioration, gene duplication, gene loss, gene fusion, gene fission, genome rearrangement, lateral gene transfer (LGT), or speciation. The other distinctive feature of ALF is its user-friendly yet powerful web interface. We illustrate the utility of ALF with two possible applications: 1) we reanalyze data from a study of selection after globin gene duplication and test the statistical significance of the original conclusions and 2) we demonstrate that LGT can dramatically decrease the accuracy of two well-established orthology inference methods. ALF is available as a stand-alone application or via a web interface at http://www.cbrg.ethz.ch/alf.     

Continuous-time modeling of cell fate determination in Arabidopsis flowers

Background  

The genetic control of floral organ specification is currently being investigated by various approaches, both experimentally and through modeling. Models and simulations have mostly involved boolean or related methods, and so far a quantitative, continuous-time approach has not been explored.     

High-performance liquid chromatographic determination of hypoxanthine and xanthine in biological fluids

A rapid and selective reversed-phase high-performance liquid chromatographic method for the simultaneous determination of hypoxanthine and xanthine in biological fluids was developed. The identification of hypoxanthine and xanthine was confirmed by xanthine oxidase reaction. This method was applied to the investigation of purine metabolism in subjects with xanthine oxidase deficiency or gout. Hypoxanthine concentrations three to ten times higher than those determined in plasma were found in erythrocyte samples from normal subjects and from patients with xanthine oxidase deficiency or hyperuricemia under allopurinol therapy.     

An analysis of the helix-to-strand transition between peptides with identical sequence

An analysis of peptide segments with identical sequence but that differ significantly in structure was performed over non-redundant databases of protein structures. We focus on those peptides, which fold into an alpha-helix in one protein but a beta-strand in another. While the study shows that many such structurally ambivalent peptides contain amino acids with a strong helical preference collocated with amino acids with a strong strand preference, the results overwhelmingly indicate that the peptide's environment ultimately dictates its structure. Furthermore, the first naturally occurring structurally ambivalent nonapeptide from evolutionary unrelated proteins is described, highlighting the intrinsic plasticity of peptide sequences. We even find seven proteins that show structural ambivalence under different conditions. Finally, a computer algorithm has been implemented to identify regions in a given sequence where secondary structure prediction programs are likely to make serious mispredictions.     

A dimensionless fit measure for phylogenetic distance trees

We present a dimensionless fit index for phylogenetic trees that have been constructed from distance matrices. It is designed to measure the quality of the fit of the data to a tree in absolute terms, independent of linear transformations on the distance matrix. The index can be used as an absolute measure to evaluate how well a set of data fits to a tree, or as a relative measure to compare different methods that are expected to produce the same tree. The usefulness of the index is demonstrated in three examples.     

Empirical codon substitution matrix

Background  

Codon substitution probabilities are used in many types of molecular evolution studies such as determining Ka/Ks ratios, creating ancestral DNA sequences or aligning coding DNA. Until the recent dramatic increase in genomic data enabled construction of empirical matrices, researchers relied on parameterized models of codon evolution. Here we present the first empirical codon substitution matrix entirely built from alignments of coding sequences from vertebrate DNA and thus provide an alternative to parameterized models of codon evolution.     

Effects of recombinant adenovirus-mediated expression of IL-2 and IL-12 in human B lymphoma cells on co-cultured PBMC

Background  

Modulation of the immune system by genetically modified lymphoma cell vaccines is of potential therapeutic value in the treatment of B cell lymphoma. However, the anti-tumor effect of any single immunogene transfer has so far been limited. Combination treatment of recombinant IL-2 and IL-12 has been reported to be synergistic for inducing anti-tumor responses in solid tumors but the potential of IL-2/IL-12 gene modified B cell lymphoma cells has not been explored yet.