Simulationen der Ausbreitung von Vulkanasche unter expliziter Berücksichtigung der optischen Eigenschaften der Aschepartikel

ICON-ART wird um die Beschreibung der optischen Eigenschaften von Vulkanasche erweitert. Dies ermöglicht die Untersuchung der Aerosol-Strahlungswechselwirkungen auf die Prozesse der synoptischen Skala. Zudem wird ein Lidar-Vorwärtsoperator implementiert, der die direkte Simulation der abgeschwächte Rückstreuung, unter berücksichtigung der Partikelform durch T-Matrix Rechnungen, erlaubt. Simulationen des Eyjafjallajökull Ausbruchs 2010 verdeutlichen die Bedeutung dieser Erweiterungen

Benchmarking of 4C-seq pipelines based on real and simulated data

"jats:sec" "jats:title"Motivation"/jats:title" "jats:p"With its capacity for high-resolution data output in one region of interest, chromosome conformation capture combined with high-throughput sequencing (4C-seq) is a state-of-the-art next-generation sequencing technique that provides epigenetic insights, and regularly advances current medical research. However, 4C-seq data are complex and prone to biases, and while specialized programs exist, an unbiased, extensive benchmarking is still lacking. Furthermore, neither substantial datasets with fully characterized ground truth, nor simulation programs for realistic 4C-seq data have been published."/jats:p" "/jats:sec" "jats:sec" "jats:title"Results"/jats:title" "jats:p"We conducted a benchmarking study on 66 4C-seq samples from 20 datasets, and developed a novel 4C-seq simulation software, Basic4CSim, to allow for detailed comparisons of 4C-seq algorithms on 50 simulated datasets with 10–120 samples each. Simulations and benchmarking were adapted to address different characteristics of 4C-seq data. Simulated data were compared with published samples to validate simulation settings. We identified differences between 4C-seq algorithms in terms of precision, recall, interaction structure, and run time, and observed general trends. Novel differential pipeline versions of single-sample based 4C-seq algorithms were included in the benchmarking. While no single tool was optimally suited for both near-cis and far-cis, and both single-sample and differential analyses, choosing a high-performing algorithm variant did improve results considerably. For near-cis scenarios, r3Cseq, peakC and FourCSeq offered high precision, while fourSig demonstrated high overall F1 scores in far-cis analyses. Finally, 4C-seq simulations may aid in the development of improved analysis algorithms."/jats:p" "/jats:sec" "jats:sec" "jats:title"Availability and implementation"/jats:title" "jats:p"Basic4CSim is available at https://github.com/walter–ca/Basic4CSim."/jats:p" "/jats:sec" "jats:sec" "jats:title"Supplementary information"/jats:title" "jats:p"Supplementary data are available at Bioinformatics online."/jats:p" "/jats:sec Document type: Articl

Long-Term Cell Tracking Following Local Injection of Mesenchymal Stromal Cells in the Equine Model of Induced Tendon Disease.

Tendon disease has been treated with multipotent mesenchymal stromal cells (MSCs) in the equine large-animal model with promising success. The aim of this study was to gain more insight into the fate and biodistribution of MSCs after local application into tendon lesions by long-term cell tracking in this large-animal model. Superficial digital flexor tendon lesions were induced in all limbs in six horses and injected with 10 × 10 6 Molday ION Rhodamine B™-labeled MSCs suspended in serum or serum alone. Follow-up was performed using low-field magnetic resonance imaging (MRI), flow cytometry, and histology. Cell tracking based on the hypointense artifacts induced by the superparamagnetic iron oxide (SPIO) labeling agent in MRI as well as based on Rhodamine B fluorescence was feasible. However, Prussian blue staining for assessment of histology was not entirely specific for SPIO. Labeled cells could be traced at their injection site by MRI as well as histology for the whole follow-up period of 24 weeks. Although the numbers of labeled cells within the injected tendon lesions decreased over time, part of the applied cells appeared to remain viable and integrated within the injured tissue. Furthermore, small numbers of labeled cells were identified in peripheral blood within the first 24 h after cell injection and could also be found until week 24 within the contralateral control tendon lesions that had been injected with serum. The present findings unveil details on MSC biodistribution and persistence after their local application, which are of clinical relevance with regard to MSC safety and mechanisms of action

Inhibition of Aromatase Induces Partial Sex Change in a Cichlid Fish: Distinct Functions for Sex Steroids in Brains and Gonads

Sex steroids are major drivers of sexual development and also responsible for the maintenance of the established gender. Especially fishes exhibit great plasticity and less conservation in sex determination and sexual development compared to other vertebrate groups. In addition, fishes have a constant sex steroid production throughout their entire lifespan, which makes them particularly susceptible to interferences with the endogenous sex steroid system. This susceptibility has recently been used to show that inhibition of the key enzyme of estrogen synthesis, aromatase Cyp19a1, can induce functional sex reversal even in adult fish. Here, we investigated the impact of the aromatase inhibitor (AI) fadrozole in adult females of the East African cichlid fish Astatotilapia burtoni. Using gene expression, phenotypic measurements, behavioral experiments, and hormone measurements, we assessed if females treated with fadrozole develop a male-like phenotype. We found that AI treatment has a different effect on gene expression in the gonad compared to the brain, the 2 tissues mostly implicated in sexual development. In contrast to observations in other gonochoristic species, A. burtoni ovaries cannot be transformed into functional testis by AI. However, rapid changes towards a male-like phenotype can be induced with AI in coloration, hormone levels, and behavior

Long-Term Cell Tracking Following Local Injection of Mesenchymal Stromal Cells in the Equine Model of Induced Tendon Disease

Tendon disease has been treated with multipotent mesenchymal stromal cells (MSCs) in the equine large-animal model with promising success. The aim of this study was to gain more insight into the fate and biodistribution of MSCs after local application into tendon lesions by long-term cell tracking in this large-animal model. Superficial digital flexor tendon lesions were induced in all limbs in six horses and injected with 10106 Molday ION Rhodamine B-labeled MSCs suspended in serum or serum alone. Follow-up was performed using low-field magnetic resonance imaging (MRI), flow cytometry, and histology. Cell tracking based on the hypointense artifacts induced by the superparamagnetic iron oxide (SPIO) labeling agent in MRI as well as based on Rhodamine B fluorescence was feasible. However, Prussian blue staining for assessment of histology was not entirely specific for SPIO. Labeled cells could be traced at their injection site by MRI as well as histology for the whole follow-up period of 24 weeks. Although the numbers of labeled cells within the injected tendon lesions decreased over time, part of the applied cells appeared to remain viable and integrated within the injured tissue. Furthermore, small numbers of labeled cells were identified in peripheral blood within the first 24 h after cell injection and could also be found until week 24 within the contralateral control tendon lesions that had been injected with serum. The present findings unveil details on MSC biodistribution and persistence after their local application, which are of clinical relevance with regard to MSC safety and mechanisms of action

Yeast Svf1 binds ceramides and contributes to sphingolipid metabolism at the ER cis-Golgi interface

Ceramides are essential precursors of complex sphingolipids and act as potent signaling molecules. Ceramides are synthesized in the endoplasmic reticulum (ER) and receive their head-groups in the Golgi apparatus, yielding complex sphingolipids (SPs). Transport of ceramides between the ER and the Golgi is executed by the essential ceramide transport protein (CERT) in mammalian cells. However, yeast cells lack a CERT homolog, and the mechanism of ER to Golgi ceramide transport remains largely elusive. Here, we identified a role for yeast Svf1 in ceramide transport between the ER and the Golgi. Svf1 is dynamically targeted to membranes via an N-terminal amphipathic helix (AH). Svf1 binds ceramide via a hydrophobic binding pocket that is located in between two lipocalin domains. We showed that Svf1 membrane-targeting is important to maintain flux of ceramides into complex SPs. Together, our results show that Svf1 is a ceramide binding protein that contributes to sphingolipid metabolism at Golgi compartments

The phosphoproteome of choroid plexus epithelial cells following infection with Neisseria meningitidis

The Gram-negative bacterium Neisseria meningitidis, which causes meningitis in humans, has been demonstrated to manipulate or alter host signalling pathways during infection of the central nervous system (CNS). However, these complex signalling networks are not completely understood. We investigate the phosphoproteome of an in vitro model of the blood-cerebrospinal fluid barrier (BCSFB) based on human epithelial choroid plexus (CP) papilloma (HIBCPP) cells during infection with the N. meningitidis serogroup B strain MC58 in presence and absence of the bacterial capsule. Interestingly, our data demonstrates a stronger impact on the phosphoproteome of the cells by the capsule-deficient mutant of MC58. Using enrichment analyses, potential pathways, molecular processes, biological processes, cellular components and kinases were determined to be regulated as a consequence of N. meningitidis infection of the BCSFB. Our data highlight a variety of protein regulations that are altered during infection of CP epithelial cells with N. meningitidis, with the regulation of several pathways and molecular events only being detected after infection with the capsule-deficient mutant. Mass spectrometry proteomics data are available via ProteomeXchange with identifier PXD038560

In Vivo Magic Angle Magnetic Resonance Imaging for Cell Tracking in Equine Low-Field MRI.

The magic angle effect increases the MRI signal of healthy tendon tissue and could be used for more detailed evaluation of tendon structure. Furthermore, it could support the discrimination of hypointense artefacts induced by contrast agents such as superparamagnetic iron oxide used for cell tracking. However, magic angle MRI of the equine superficial digital flexor tendon has not been accomplished in vivo in standing low-field MRI so far. The aim of this in vivo study was to evaluate the practicability of this magic angle technique and its benefit for tracking superparamagnetic iron oxide-labelled multipotent mesenchymal stromal cells. Six horses with induced tendinopathy in their forelimb superficial digital flexor tendons were injected locally either with superparamagnetic iron oxide-labelled multipotent mesenchymal stromal cells or serum. MRI included standard and magic angle image series in T1- and T2∗-weighted sequences performed at regular intervals. Image analysis comprised blinded evaluation and quantitative assessment of signal-to-noise ratio. The magic angle technique enhanced the tendon signal-to-noise ratio (P < 0.001). Hypointense artefacts were observable in the cell-injected superficial digital flexor tendons over 24 weeks and artefact signal-to-noise ratio differed significantly from tendon signal-to-noise ratio in the magic angle images (P < 0.001). Magic angle imaging of the equine superficial digital flexor tendon is feasible in standing low-field MRI. The current data demonstrate that the technique improves discrimination of superparamagnetic iron oxide-induced artefacts from the surrounding tendon tissue.Peer Reviewe

GeneTrail 3: advanced high-throughput enrichment analysis

We present GeneTrail 3, a major extension of our web service GeneTrail that offers rich functionality for the identification, analysis, and visualization of deregulated biological processes. Our web service provides a comprehensive collection of biological processes and signaling pathways for 12 model organisms that can be analyzed with a powerful framework for enrichment and network analysis of transcriptomic, miRNomic, proteomic, and genomic data sets. Moreover, GeneTrail offers novel workflows for the analysis of epigenetic marks, time series experiments, and single cell data. We demonstrate the capabilities of our web service in two case-studies, which highlight that GeneTrail is well equipped for uncovering complex molecular mechanisms. GeneTrail is freely accessible at: http://genetrail.bioinf.uni-sb.de