Microarray-Based Gene Expression Analysis of Hepatocellular Carcinoma

Microarray studies have successfully shed light on various aspects of the molecular mechanisms behind the development of hepatocellular carcinoma (HCC), such as the identification of novel molecular subgroups and the genetic profiles associated with metastasis and venous invasion. These experiments, mainly comprising genome wide profiling, potentially represent the basis of novel targeted therapeutic strategies in HCC. In response, we summarize the multiple reported expression profiles in HCC associated with HCC development, novel subgroups, venous invasion and metastasis

Identification of a Putative Crf Splice Variant and Generation of Recombinant Antibodies for the Specific Detection of Aspergillus fumigatus

BACKGROUND: Aspergillus fumigatus is a common airborne fungal pathogen for humans. It frequently causes an invasive aspergillosis (IA) in immunocompromised patients with poor prognosis. Potent antifungal drugs are very expensive and cause serious adverse effects. Their correct application requires an early and specific diagnosis of IA, which is still not properly achievable. This work aims to a specific detection of A. fumigatus by immunofluorescence and the generation of recombinant antibodies for the detection of A. fumigatus by ELISA. RESULTS: The A. fumigatus antigen Crf2 was isolated from a human patient with proven IA. It is a novel variant of a group of surface proteins (Crf1, Asp f9, Asp f16) which belong to the glycosylhydrolase family. Single chain fragment variables (scFvs) were obtained by phage display from a human naive antibody gene library and an immune antibody gene library generated from a macaque immunized with recombinant Crf2. Two different selection strategies were performed and shown to influence the selection of scFvs recognizing the Crf2 antigen in its native conformation. Using these antibodies, Crf2 was localized in growing hyphae of A. fumigatus but not in spores. In addition, the antibodies allowed differentiation between A. fumigatus and related Aspergillus species or Candida albicans by immunofluorescence microscopy. The scFv antibody clones were further characterized for their affinity, the nature of their epitope, their serum stability and their detection limit of Crf2 in human serum. CONCLUSION: Crf2 and the corresponding recombinant antibodies offer a novel approach for the early diagnostics of IA caused by A. fumigatus

The functional cancer map: A systems-level synopsis of genetic deregulation in cancer

<p>Abstract</p> <p>Background</p> <p>Cancer cells are characterized by massive dysegulation of physiological cell functions with considerable disruption of transcriptional regulation. Genome-wide transcriptome profiling can be utilized for early detection and molecular classification of cancers. Accurate discrimination of functionally different tumor types may help to guide selection of targeted therapy in translational research. Concise grouping of tumor types in cancer maps according to their molecular profile may further be helpful for the development of new therapeutic modalities or open new avenues for already established therapies.</p> <p>Methods</p> <p>Complete available human tumor data of the Stanford Microarray Database was downloaded and filtered for relevance, adequacy and reliability. A total of 649 tumor samples from more than 1400 experiments and 58 different tissues were analyzed. Next, a method to score deregulation of KEGG pathway maps in different tumor entities was established, which was then used to convert hundreds of gene expression profiles into corresponding tumor-specific pathway activity profiles. Based on the latter, we defined a measure for functional similarity between tumor entities, which yielded to phylogeny of tumors.</p> <p>Results</p> <p>We provide a comprehensive, easy-to-interpret functional cancer map that characterizes tumor types with respect to their biological and functional behavior. Consistently, multiple pathways commonly associated with tumor progression were revealed as common features in the majority of the tumors. However, several pathways previously not linked to carcinogenesis were identified in multiple cancers suggesting an essential role of these pathways in cancer biology. Among these pathways were 'ECM-receptor interaction', 'Complement and Coagulation cascades', and 'PPAR signaling pathway'.</p> <p>Conclusion</p> <p>The functional cancer map provides a systematic view on molecular similarities across different cancers by comparing tumors on the level of pathway activity. This work resulted in identification of novel superimposed functional pathways potentially linked to cancer biology. Therefore, our work may serve as a starting point for rationalizing combination of tumor therapeutics as well as for expanding the application of well-established targeted tumor therapies.</p

The genomic and transcriptional landscape of primary central nervous system lymphoma

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations

Reflexionen von Machterfahrungen in der eigenen Schulkarriere

Die Autor*innen bearbeiten in ihrem Beitrag auf Grundlage einer Gruppendiskussion mit Studierenden aus dem Seminar ,Macht und Privilegien in der Schule‘ die Relevanz der „Reflexion von Machterfahrungen in der eigenen Schulkarriere“. Es wird deutlich, dass die meisten Schüler*innen über Erfahrungen mit Macht und Ohnmacht verfügen und diese auch in der eigenen Schulkarriere erlebt haben. Die Autor*innen stellen heraus, dass (angehende) Lehrkräfte sich der herrschenden hierarchischen Struktur in Schule bewusst sein müssen und diese, sich selbst sowie ihre eigene pädagogische Praxis reflektieren sollten. (DIPF/Orig.

Demography of the giant otter (Pteronura brasiliensis) in Manu National Park, south-eastern Peru: implications for conservation.

The giant otter (Pteronura brasiliensis) is an endangered semi-aquatic carnivore of South America. We present findings on the demography of a population inhabiting the floodplain of Manu National Park, south-eastern Peru, arising from 14 annual dry season censuses over a 16 year period. The breeding system of territorial groups, including only a single breeding female with non-reproductive adult 'helpers', resulted in a low intrinsic rate of increase (0.03) and a slow recovery from decades of hunting for the pelt trade. This is explained by a combination of factors: (1) physiological traits such as late age at first reproduction and long generation time, (2) a high degree of reproductive skew, (3) small litters produced only once a year, and (4) a 50% mortality between den emergence and age of dispersal, as well as high mortality amongst dispersers (especially males). Female and male giant otters show similar traits with respect to average reproductive life-spans (female 5.4 yrs., male 5.2 yrs.) and average cub productivity (female 6.9, male 6.7 cubs per lifetime); the longest reproductive life spans were 11 and 13 years respectively. Individual reproductive success varied substantially and depended mainly on the duration of dominance tenure in the territory. When breeding females died, the reproductive position in the group was usually occupied by sisters or daughters (n = 11), with immigrant male partners. Male philopatry was not observed. The vulnerability of the Manu giant otter population to anthropogenic disturbance emphasises the importance of effective protection of core lake habitats in particular. Riverine forests are the most endangered ecosystem in the Department of Madre de Dios due to the concentration of gold mining, logging and agricultural activities in floodplains, highlighting the need for a giant otter habitat conservation corridor along the Madre de Dios River