Repressionen gegen Ägyptens Zivilgesellschaft: staatliche Gewalt, Verengung des öffentlichen Raums und außergesetzliche Verfolgung

"Seit dem Militärputsch im Juli 2013 zeichnet sich das ägyptische Regime unter anderem dadurch aus, dass die Grenzen dessen, was an politischen Aktivitäten zulässig ist, nicht klar definiert werden. Die graduelle Verengung des öffentlichen Raums durch immer neue Präsidialdekrete zeigt vielmehr, dass sich die roten Linien jederzeit verschieben können. Dazu kommt in immer stärkerem Maße ein Missbrauch der Staatsgewalt gegen Vertreterinnen und Vertreter der ägyptischen Zivilgesellschaft, etwa in Form von Folter und Zwangsverschleppungen. Menschenrechtsaktivisten werden hierbei zunehmend von Zeugen zu Opfern von Übergriffen. Im Visier der Staatssicherheit, einer politisierten Judikative und konkurrierender Ministerien können sie ihre Rolle als Watchdogs immer weniger ausfüllen. Deutschland sollte sich vor diesem Hintergrund gemeinsam mit seinen europäischen Partnern für die Wahrung bürgerlicher Grundrechte und rechtsstaatlicher Standards in Ägypten einsetzen und seine Unterstützung stärker auf den Bedarf ägyptischer Nichtregierungsorganisationen abstimmen." (Autorenreferat

Molecular subtypes of osteosarcoma identified by reducing tumor heterogeneity through an interspecies comparative approach

The heterogeneous and chaotic nature of osteosarcoma has confounded accurate molecular classification, prognosis, and prediction for this tumor. The occurrence of spontaneous osteosarcoma is largely confined to humans and dogs. While the clinical features are remarkably similar in both species, the organization of dogs into defined breeds provides a more homogeneous genetic background that may increase the likelihood to uncover molecular subtypes for this complex disease. We thus hypothesized that molecular profiles derived from canine osteosarcoma would aid in molecular subclassification of this disease when applied to humans. To test the hypothesis, we performed genome wide gene expression profiling in a cohort of dogs with osteosarcoma, primarily from high-risk breeds. To further reduce inter-sample heterogeneity, we assessed tumor-intrinsic properties through use of an extensive panel of osteosarcoma-derived cell lines. We observed strong differential gene expression that segregated samples into two groups with differential survival probabilities. Groupings were characterized by the inversely correlated expression of genes associated with G2/M transition and DNA damage checkpoint and microenvironment-interaction categories. This signature was preserved in data from whole tumor samples of three independent dog osteosarcoma cohorts, with stratification into the two expected groups. Significantly, this restricted signature partially overlapped a previously defined, predictive signature for soft tissue sarcomas, and it unmasked orthologous molecular subtypes and their corresponding natural histories in five independent data sets from human patients with osteosarcoma. Our results indicate that the narrower genetic diversity of dogs can be utilized to group complex human osteosarcoma into biologically and clinically relevant molecular subtypes. This in turn may enhance prognosis and prediction, and identify relevant therapeutic targets

Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states

<p>Abstract</p> <p>Background</p> <p>Colon cancer arises from the accumulation of multiple genetic and epigenetic alterations to normal colonic tissue. microRNAs (miRNAs) are small, non-coding regulatory RNAs that post-transcriptionally regulate gene expression. Differential miRNA expression in cancer versus normal tissue is a common event and may be pivotal for tumor onset and progression.</p> <p>Methods</p> <p>To identify miRNAs that are differentially expressed in tumors and tumor subtypes, we carried out highly sensitive expression profiling of 735 miRNAs on samples obtained from a statistically powerful set of tumors (n = 80) and normal colon tissue (n = 28) and validated a subset of this data by qRT-PCR.</p> <p>Results</p> <p>Tumor specimens showed highly significant and large fold change differential expression of the levels of 39 miRNAs including miR-135b, miR-96, miR-182, miR-183, miR-1, and miR-133a, relative to normal colon tissue. Significant differences were also seen in 6 miRNAs including miR-31 and miR-592, in the direct comparison of tumors that were deficient or proficient for mismatch repair. Examination of the genomic regions containing differentially expressed miRNAs revealed that they were also differentially methylated in colon cancer at a far greater rate than would be expected by chance. A network of interactions between these miRNAs and genes associated with colon cancer provided evidence for the role of these miRNAs as oncogenes by attenuation of tumor suppressor genes.</p> <p>Conclusion</p> <p>Colon tumors show differential expression of miRNAs depending on mismatch repair status. miRNA expression in colon tumors has an epigenetic component and altered expression that may reflect a reversion to regulatory programs characteristic of undifferentiated proliferative developmental states.</p

Growth enhancement and food conversion efficiency of transgenic fish Labeo rohita

Three family lines of fast growing transgenic rohu Labeo rohita (rohu) were generated by electroporated-sperm-mediated transfer of the vectors harboring CMV promoter or grass carp β-actin promoter fused to endogenous rohu GH (rGH) cDNA. The gene transfer efficiency was 25%. The transgenic rohu (family line 1) with CMV promoter showed a growth enhancement of four times normal size, whereas those (family lines 2 and 3) generated with β-actin promoter grew 4.5 and 5.8 times faster than their respective control siblings. Southern analysis confirmed the transgene extrachromosomal (Te) persistence until the 60th week in family 1. The individuals of family lines 2 and 3, however, showed integration (Ti), as well as persistence as extarchromosomal copies (Te) until the age of 30 weeks. Mosaicism of the transgene was shown at the levels of its presence and expression. The ectopic expression of rGH mRNA was confirmed by RT-PCR. Feeding experiments revealed that the transgenic rohu ate food at a lower rate but grew more efficiently than their control siblings

Minnelide reduces tumor burden in preclinical models of osteosarcoma

•Triptolide induces significant apoptosis in osteosarcoma cell lines with minimal effect on osteoblast cells.•Triptolide downregulates multiple pro-survival genes and pathways that contribute to osteosarcoma progression.•Minnelide reduces tumor burden in orthotopic model of osteosarcoma.•Minnelide decreases metastasis in lung colonization model. Osteosarcoma is the most common bone cancer in children and adolescents with a 5-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on osteosarcoma. Triptolide was effective in significantly inducing apoptosis in all osteosarcoma cell lines tested but had no significant effect on the human osteoblast cells. Notably, Minnelide treatment significantly reduced tumor burden and lung metastasis in the orthotopic and lung colonization models. Triptolide/Minnelide effectively downregulated the levels of pro-survival proteins such as heat shock proteins, cMYC, survivin and targets the NF-κB pathway

Additional file 3: Figure S3. of A transwell assay that excludes exosomes for assessment of tunneling nanotube-mediated intercellular communication

Validation of exosome recovery. VAMT exosomes (2 × 109) were added into 6- well plates containing 2 ml of serum free basal mTeSR1 medium and incubated for 48 h. After 48 h, medium was collected and subjected to exosome isolation for NTA. Almost all of the 2 × 109 exosomes added were recovered without a significant loss, with a recovery efficiency of >95%. The exosome samples were run 5 times and averaged. SD is shown as the error bar. (TIFF 1107 kb

Additional file 4: Figure S4. of A transwell assay that excludes exosomes for assessment of tunneling nanotube-mediated intercellular communication

Uptake of exosomes crossing the transwell membrane is significantly decreased by heparin treatment of recipient cells. PKH26 (Red) labelled VAMT exosomes were added to MSTO cells pre-treated with (b) or without (a) 10 μg/mL heparin. Exosome uptake was analyzed after 24 h of culture. DIC and DIC + fluorescent merged images of control and heparin-treated cells are shown. (TIFF 2404 kb

Combinatorial Treatment of DNA and Chromatin- Modifying Drugs Cause Cell Death in Human and Canine

Downregulation of microRNAs (miRNAs) at the 14q32 locus stabilizes the expression of cMYC, thus significantly contributing to osteosarcoma (OS) pathobiology. Here, we show that downregulation of 14q32 miRNAs is epigenetically regulated. The predicted promoter regions of miRNA clusters at 14q32 locus showed no recurrent patterns of differential methylation, but Saos2 cells showed elevated histone deacetylase (HDAC) activity. Treatment with 4-phenylbutyrate increased acetylation of histones associated with 14q32 miRNAs, but interestingly, robust restoration of 14q32 miRNA expression, attenuation of cMYC expression, and induction of apoptosis required concomitant treatment with 5-Azacytidine, an inhibitor of DNA methylation. These events were associated with genome-wide gene expression changes including induction of pro-apoptotic genes and downregulation of cell cycle genes. Comparable effects were achieved in human and canine OS cells using the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA/Vorinostat) and the DNA methylation inhibitor Zebularine (Zeb), with significantly more pronounced cytotoxicity in cells whose molecular phenotypes were indicative of aggressive biological behavior. These results suggested that the combination of these chromatin-modifying drugs may be a usefu