Chylous ascites and chylothorax: a case study

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A social role for churches and cultural demarcation:how German MEPs represent religion in the European Parliament

This study deals with the question of how German members of the European Parliament (MEPs) represent the German model of religion–state relations at the European level. Based on a survey and interviews with German MEPs as well as a content-analysis of German MEPs’ speeches, motions and parliamentary questions during the seventh term of the European Parliament (EP), our study demonstrates that this model is represented in three dimensions. First, German MEPs reflect the close cooperation between the churches and the state in Germany, primarily on social issues, through largely church- and religion-friendly attitudes and relatively frequent contacts with religious interest-groups. Second, by referring to religious freedoms and minorities primarily outside the EU and by placing Islam in considerably more critical contexts than Christianity, German MEPs create a cultural demarcation line between Islam and Christianity through their parliamentary activities, which is similar to, though less politicised than, cultural boundaries often produced in public debates in Germany. Third, our study illustrates similar patterns of religious affiliation and subjective religiosity among German parliamentarians in both the EP and the national Parliament, which to some degree also reflect societal trends in Germany. Yet our data also suggest that European political elites are more religious than the average German population. If the presence of religion in terms of religious interest-groups and arguments is included, the EP appears to be more secularist than the German Parliament

Minimally Invasive Surgical Approaches and Traditional Total Hip Arthroplasty: A Meta-Analysis of Radiological and Complications Outcomes

BACKGROUND: Minimally invasive total hip arthroplasty (MITHA) remains considerably controversial. Limited visibility and prosthesis malposition increase the risk of post-surgical complications compared to those of the traditional method. METHODS: A meta-analysis was undertaken of all published databases up to May 2011. The studies were divided into four subgroups according to the surgical approach taken. The radiological outcomes and complications of minimally invasive surgery were compared to traditional total hip arthroplasty (TTHA) using risk ratio, mean difference, and standardized mean difference statistics. RESULTS: In five studies involving the posterolateral approach, no significant differences were found between the MITHA groups and the TTHA groups in the acetabular cup abduction angle (p = 0.41), acetabular anteversion (p = 0.96), and femoral prosthesis position (p = 0.83). However, the femoral offset was significantly increased (WMD = 3.00; 95% CI, 0.40-5.60; p = 0.02). Additionally, there were no significant differences among the complications in both the groups (dislocations, nerve injury, infection, deep vein thrombosis, proximal femoral fracture) and revision rate (p>0.05). In three studies involving the posterior approach, there were no significant differences in radiological outcomes or all other complications between MITHA or TTHA groups (p>0.05). Three studies involved anterolateral approach, while 2 studies used the lateral approach. However, the information from imaging and complications was not adequate for statistical analysis. CONCLUSIONS: Posterior MITHA seems to be a safe surgical procedure, without the increased risk of post-operative complication rates and component malposition rates. The posterolateral approach THA may lead to increased femoral offset. The current data are not enough to reach a positive conclusion that lateral and anterolateral approaches will result in increased risks of adverse effects and complications at the prosthesis site

Omeprazole Inhibits Proliferation and Modulates Autophagy in Pancreatic Cancer Cells

BACKGROUND: Omeprazole has recently been described as a modulator of tumour chemoresistance, although its underlying molecular mechanisms remain controversial. Since pancreatic tumours are highly chemoresistant, a logical step would be to investigate the pharmacodynamic, morphological and biochemical effects of omeprazole on pancreatic cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: Dose-effect curves of omeprazole, pantoprazole, gemcitabine, 5-fluorouracil and the combinations of omeprazole and 5-fluorouracil or gemcitabine were generated for the pancreatic cancer cell lines MiaPaCa-2, ASPC-1, Colo357, PancTu-1, Panc1 and Panc89. They revealed that omeprazole inhibited proliferation at probably non-toxic concentrations and reversed the hormesis phenomena of 5-fluorouracil. Electron microscopy showed that omeprazole led to accumulation of phagophores and early autophagosomes in ASPC-1 and MiaPaCa-2 cells. Signal changes indicating inhibited proliferation and programmed cell death were found by proton NMR spectroscopy of both cell lines when treated with omeprazole which was identified intracellularly. Omeprazole modulates the lysosomal transport pathway as shown by Western blot analysis of the expression of LAMP-1, Cathepsin-D and β-COP in lysosome- and Golgi complex containing cell fractions. Acridine orange staining revealed that the pump function of the vATPase was not specifically inhibited by omeprazole. Gene expression of the autophagy-related LC3 gene as well as of Bad, Mdr-1, Atg12 and the vATPase was analysed after treatment of cells with 5-fluorouracil and omeprazole and confirmed the above mentioned results. CONCLUSIONS: We hypothesise that omeprazole interacts with the regulatory functions of the vATPase without inhibiting its pump function. A modulation of the lysosomal transport pathway and autophagy is caused in pancreatic cancer cells leading to programmed cell death. This may circumvent common resistance mechanisms of pancreatic cancer. Since omeprazole use has already been established in clinical practice these results could lead to new clinical applications

Stability of domain structures in multi-domain proteins

Multi-domain proteins have many advantages with respect to stability and folding inside cells. Here we attempt to understand the intricate relationship between the domain-domain interactions and the stability of domains in isolation. We provide quantitative treatment and proof for prevailing intuitive ideas on the strategies employed by nature to stabilize otherwise unstable domains. We find that domains incapable of independent stability are stabilized by favourable interactions with tethered domains in the multi-domain context. Stability of such folds to exist independently is optimized by evolution. Specific residue mutations in the sites equivalent to inter-domain interface enhance the overall solvation, thereby stabilizing these domain folds independently. A few naturally occurring variants at these sites alter communication between domains and affect stability leading to disease manifestation. Our analysis provides safe guidelines for mutagenesis which have attractive applications in obtaining stable fragments and domain constructs essential for structural studies by crystallography and NMR

Genetic Rearrangements Can Modify Chromatin Features at Epialleles

Analogous to genetically distinct alleles, epialleles represent heritable states of different gene expression from sequence-identical genes. Alleles and epialleles both contribute to phenotypic heterogeneity. While alleles originate from mutation and recombination, the source of epialleles is less well understood. We analyze active and inactive epialleles that were found at a transgenic insert with a selectable marker gene in Arabidopsis. Both converse expression states are stably transmitted to progeny. The silent epiallele was previously shown to change its state upon loss-of-function of trans-acting regulators and drug treatments. We analyzed the composition of the epialleles, their chromatin features, their nuclear localization, transcripts, and homologous small RNA. After mutagenesis by T-DNA transformation of plants carrying the silent epiallele, we found new active alleles. These switches were associated with different, larger or smaller, and non-overlapping deletions or rearrangements in the 3′ regions of the epiallele. These cis-mutations caused different degrees of gene expression stability depending on the nature of the sequence alteration, the consequences for transcription and transcripts, and the resulting chromatin organization upstream. This illustrates a tight dependence of epigenetic regulation on local structures and indicates that sequence alterations can cause epigenetic changes at some distance in regions not directly affected by the mutation. Similar effects may also be involved in gene expression and chromatin changes in the vicinity of transposon insertions or excisions, recombination events, or DNA repair processes and could contribute to the origin of new epialleles

Comparative Genomic and Transcriptomic Characterization of the Toxigenic Marine Dinoflagellate Alexandrium ostenfeldii

Many dinoflagellate species are notorious for the toxins they produce and ecological and human health consequences associated with harmful algal blooms (HABs). Dinoflagellates are particularly refractory to genomic analysis due to the enormous genome size, lack of knowledge about their DNA composition and structure, and peculiarities of gene regulation, such as spliced leader (SL) trans-splicing and mRNA transposition mechanisms. Alexandrium ostenfeldii is known to produce macrocyclic imine toxins, described as spirolides. We characterized the genome of A. ostenfeldii using a combination of transcriptomic data and random genomic clones for comparison with other dinoflagellates, particularly Alexandrium species. Examination of SL sequences revealed similar features as in other dinoflagellates, including Alexandrium species. SL sequences in decay indicate frequent retro-transposition of mRNA species. This probably contributes to overall genome complexity by generating additional gene copies. Sequencing of several thousand fosmid and bacterial artificial chromosome (BAC) ends yielded a wealth of simple repeats and tandemly repeated longer sequence stretches which we estimated to comprise more than half of the whole genome. Surprisingly, the repeats comprise a very limited set of 79–97 bp sequences; in part the genome is thus a relatively uniform sequence space interrupted by coding sequences. Our genomic sequence survey (GSS) represents the largest genomic data set of a dinoflagellate to date. Alexandrium ostenfeldii is a typical dinoflagellate with respect to its transcriptome and mRNA transposition but demonstrates Alexandrium-like stop codon usage. The large portion of repetitive sequences and the organization within the genome is in agreement with several other studies on dinoflagellates using different approaches. It remains to be determined whether this unusual composition is directly correlated to the exceptionally genome organization of dinoflagellates with a low amount of histones and histone-like proteins