Kurzanalyse 4: Bürgschaften für die Finanzierung von Aktivitäten zur Steigerung der Ressourceneffizienz von KMU

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RNA-Seq analysis of soft rush (Juncus effusus): transcriptome sequencing, de novo assembly, annotation, and polymorphism identification

Background: Juncus effusus L. (family: Juncaceae; order: Poales) is a helophytic rush growing in temperate damp or wet terrestrial habitats and is of almost cosmopolitan distribution. The species has been studied intensively with respect to its interaction with co-occurring plants as well as microbes being involved in major biogeochemical cycles. J. effusus has biotechnological value as component of Constructed Wetlands where the plant has been employed in phytoremediation of contaminated water. Its genome has not been sequenced. Results: In this study we carried out functional annotation and polymorphism analysis of de novo assembled RNA-Seq data from 18 genotypes using 249 million paired-end Illumina HiSeq reads and 2.8 million 454 Titanium reads. The assembly comprised 158,591 contigs with a mean contig length of 780bp. The assembly was annotated using the dammit! annotation pipeline, which queries the databases OrthoDB, Pfam-A, Rfam, and runs BUSCO (Benchmarking Single-Copy Ortholog genes). In total, 111,567 contigs (70.3%) were annotated with functional descriptions, assigned gene ontology terms, and conserved protein domains, which resulted in 30,932 non-redundant gene sequences. Results of BUSCO and KEGG pathway analyses were similar for J. effusus as for the well-studied members of the Poales, Oryza sativa and Sorghum bicolor. A total of 566,433 polymorphisms were identified in transcribed regions with an average frequency of 1 polymorphism in every 171 bases. Conclusions: The transcriptome assembly was of high quality and genome coverage was sufficient for global analyses. This annotated knowledge resource can be utilized for future gene expression analysis, genomic feature comparisons, genotyping, primer design, and functional genomics in J. effusus.German Academic Exchange Program (DAAD); German Science Foundation (DFG) [MI 1500/2-1]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Highly parallel assays of tissue-specific enhancers in whole Drosophila embryos

Transcriptional enhancers are a primary mechanism by which tissue-specific gene expression is achieved. Despite the importance of these regulatory elements in development, responses to environmental stresses, and disease, testing enhancer activity in animals remains tedious, with a minority of enhancers having been characterized. Here, we have developed ‘enhancer-FACS-Seq’ (eFS) technology for highly parallel identification of active, tissue-specific enhancers in Drosophila embryos. Analysis of enhancers identified by eFS to be active in mesodermal tissues revealed enriched DNA binding site motifs of known and putative, novel mesodermal transcription factors (TFs). Naïve Bayes classifiers using TF binding site motifs accurately predicted mesodermal enhancer activity. Application of eFS to other cell types and organisms should accelerate the cataloging of enhancers and understanding how transcriptional regulation is encoded within them

Inability of shear-wave elastography to distinguish malignant from benign prostate tissue – a comparison of biopsy, whole-mount sectioning and shear-wave elastography

Aim: This study was designed to assess the possible usefulness of shear-wave elastography in differentiating between benign and malignant tissue in prostate neoplasia. Patients and methods: A total of 120 prostate tissue samples were obtained from 10 patients treated by radical prostatectomy and investigated pre-operatively by ultrasound elastography followed by directed biopsy. After resection, whole-mount sectioning and histological examination was performed. The predictions based on shear-wave elastography were compared with biopsy and histological results. Results: The comparison between the results of shear-wave elastography and those of biopsy was performed by receiver operating characteristic analysis, which suggested an optimum cut-off tissue elasticity value of 50 kPa, in agreement with earlier studies aimed at distinguishing between benign and malignant tissue. However, the diagnostic selectivity (and thus the diagnostic power) was poor (area under the curve 0.527, which hardly differs from the value of 0.500 that would correspond to a complete lack of predictive power); furthermore, application of this cut-off value to the samples led to a sensitivity of only 74% and a specificity of only 43%. An analogous comparison between the results of shear-wave elastography and those of whole-mount histology, which itself is more reliable than biopsy, gave an even poorer diagnostic selectivity (sensitivity of 62%, specificity of 35%). Meaningful association with Gleason score was not found for D'Amico risk groups (p = 0.35). Conclusions: The (negative) findings of this investigation add to the dissonance among results of studies investigating the possible value of shear-wave elastography as a diagnostic tool to identify malignant neoplasia. There is a clear need for further research to elucidate the diversity of study results and to identify the usefulness, if any, of the method in question

Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors.

BACKGROUND Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs. METHODS In this prospective multi-center study, we combined a multi-omics approach including unbiased single-cell profiling of over 300 peripheral blood mononuclear cell (PBMC) samples and high-throughput proteomics analysis of over 500 serum samples to characterize the systemic immune compartment of patients with melanoma or NSCLC before and during treatment with ICIs. FINDINGS When we combined the parameters obtained from the multi-omics profiling of patient blood and serum, we identified potential predictive biomarkers for ICI-induced irAEs. Specifically, an early increase in CXCL9/CXCL10/CXCL11 and interferon-γ (IFN-γ) 1 to 2 weeks after the start of therapy are likely indicators of heightened risk of developing irAEs. In addition, an early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells is also likely to be associated with increased risk of irAEs. CONCLUSIONS We suggest that the combination of these cellular and proteomic biomarkers may help to predict which patients are likely to benefit most from ICI therapy and those requiring intensive monitoring for irAEs. FUNDING This work was primarily funded by the European Research Council, the Swiss National Science Foundation, the Swiss Cancer League, and the Forschungsförderung of the Kantonsspital St. Gallen

Environmentally relevant concentrations of citalopram partially inhibit feeding in the three-spine stickleback (Gasterosteus aculeatus)

Selective Serotonin Re-uptake Inhibitors (SSRI) are mood-altering, psychotropic drugs commonly used in the treatment of depression and other psychological illnesses. Many of them are poorly degraded in sewage treatment plants and enter the environment unaltered. In laboratory studies, they have been demonstrated to affect a wide range of behaviours in aquatic organisms. In this study we investigated the effect of a three-week exposure to 0.15 and 1.5 μg/l of the SSRI citalopram dissolved in the ambient water on the feeding behaviour in three-spine stickleback (Gasterosteus aculeatus). Feeding, measured as the number of attacks performed on a piece of frozen bloodworms during a 10-min period, was reduced by 30–40% in fish exposed to both 0.15 and 1.5 μg/l citalopram. The effects of the environmentally relevant concentration 0.15 μg/l on feeding, an important fitness characteristic, suggests that the ecological significance of environmental SSRI exposure may be pronounced

New aspects in shear-wave elastography of prostate cancer

Aim: This study was designed to evaluate the performance of shear-wave elastography as a diagnostic tool for prostate cancer in a larger cohort of patients than previously reported. Patients and methods: Seventy-three patients with suspected prostate carcinoma were investigated by ultrasound elastography followed by directed biopsy. The elastographic and histological results for all biopsies were compared. Results: After exclusion of invalid and non-assessable results, 794 samples were obtained for which both a histological assessment and an elastometric result (tissue stiffness in kPa) were available: according to the histology 589 were benign and 205 were malignant. Tissue elasticity was found to be weakly correlated with patient’s age, PSA level and gland volume. ROC analysis showed that, for the set of results acquired, elastometry did not fulfi l literature claims that it could identify malignant neoplasia with high sensitivity and specifi city. However, it did show promise in distinguishing between Gleason scores ≤6 and >6 when malignancy had already been identifi ed. Unexpected observations were the fi nding of a smaller proportion of tumours in the lateral regions of the prostate than generally expected, and also the observation that the elasticity of benign prostate tissue is region-sensitive, the tissue being stiffest in the basal region and more elastic at the apex. Conclusions: Shear-wave elastography was found to be a poor predictor of malignancy, but for malignant lesions an elasticity cut-off of 80 kPa allowed a fairly reliable distinction between lesions with Gleason ≤6 and those with Gleason >6. We demonstrate an increase in elasticity of benign prostate tissue from the basal to the apical region.Cel: Badanie przeprowadzono w celu ustalenia wartości diagnostycznej elastografi i fali poprzecznej w raku stercza, analizując większą grupę chorych, niż dotychczas przedstawiano w piśmiennictwie. Pacjenci i metoda: Badaniem objęto 73 pacjentów z podejrzeniem raka stercza. Ocenę gruczołu krokowego wykonywano za pomocą elastografi i, po której stosowano biopsję celowaną. Wyniki: Po wykluczeniu nieważnych i trudnych do oceny wyników uzyskano 794 przypadki, które oceniono zarówno histopatologicznie, jak i metodą elastografi i (sztywność tkanek mierzona w kPa), stwierdzając w badaniu histopatologicznym 589 zmian łagodnych i 205 złośliwych. Wykazano słabą korelację sprężystości tkanek z wiekiem chorych, poziomem PSA i objętością gruczołu krokowego. Analiza ROC otrzymanych wyników udowodniła, że elastometria w diagnostyce ognisk złośliwego nowotworzenia nie jest tak czułą i swoistą metodą, jak zakładano w piśmiennictwie. W przypadkach, w których zdiagnozowano proces złośliwy, metoda ta umożliwia rozróżnienie ognisk ocenianych w skali Gleasona ≤6 od tych >6 punktów. Te nieoczekiwane obserwacje dotyczyły mniejszego odsetka nowotworów, niż wcześniej zakładano, położonych w bocznych częściach prostaty. Ponadto zaobserwowano zależność między poziomem sprężystości tkanek objętych procesem łagodnym w poszczególnych częściach gruczołu krokowego: największą sztywność wykazano w części podstawnej, a większą sprężystość w części wierzchołkowej. Wnioski: Elastografi a fali poprzecznej jest słabym predyktorem złośliwości, chociaż w diagnostyce ognisk złośliwych, z punktem odcięcia poziomu sprężystości wynoszącym 80 kPA, umożliwia dość wiarygodne zróżnicowanie zmian o stopniu zaawansowania ≤6 punktów i zmian o stopniu zaawansowania >6 punktów w skali Gleasona

Circular Abscess Formation of the Inner Preputial Leaf as a Complication of a Penile Mondor's Disease: The First Case Report

Introduction. Mondor's disease of the penis is an uncommon condition characterized by thrombosis or thrombophlebitis involving the superficial dorsal veins. An accompanied lymphangitis is discussed. There is typical self-limiting clinical course. Case Presentation. This paper firstly reports a secondary abscess formation of the preputial leaf two weeks after penile Mondor's disease and subcutaneous lymphangitis as complication of excessive sexual intercourse of a 44-year-old man. Sexual transmitted diseases could be excluded. Lesions healed up completely under abscess drainage, antibiotic, and anti-inflammatory medication. Conclusion. Previous reports in the literature include several entities of the penile Mondor's disease. Our patient is very unusual in that he presented with a secondary preputial abscess formation due to superficial thrombophlebitis, subcutaneous lymphangitis, and local bacterial colonisation. Abscess drainage plus antiphlogistic and antibiotic medication is the treatment of choice