يعرض 1 - 10 نتائج من 397 نتيجة بحث عن '"Ralf Zimmer"', وقت الاستعلام: 0.80s تنقيح النتائج
  1. 1
    دورية أكاديمية

    المصدر: eLife, Vol 12 (2024)

    الوصف: Cardiac macrophages are heterogenous in phenotype and functions, which has been associated with differences in their ontogeny. Despite extensive research, our understanding of the precise role of different subsets of macrophages in ischemia/reperfusion (I/R) injury remains incomplete. We here investigated macrophage lineages and ablated tissue macrophages in homeostasis and after I/R injury in a CSF1R-dependent manner. Genomic deletion of a fms-intronic regulatory element (FIRE) in the Csf1r locus resulted in specific absence of resident homeostatic and antigen-presenting macrophages, without affecting the recruitment of monocyte-derived macrophages to the infarcted heart. Specific absence of homeostatic, monocyte-independent macrophages altered the immune cell crosstalk in response to injury and induced proinflammatory neutrophil polarization, resulting in impaired cardiac remodeling without influencing infarct size. In contrast, continuous CSF1R inhibition led to depletion of both resident and recruited macrophage populations. This augmented adverse remodeling after I/R and led to an increased infarct size and deterioration of cardiac function. In summary, resident macrophages orchestrate inflammatory responses improving cardiac remodeling, while recruited macrophages determine infarct size after I/R injury. These findings attribute distinct beneficial effects to different macrophage populations in the context of myocardial infarction.

    وصف الملف: electronic resource

  2. 2
    دورية أكاديمية

    المصدر: Computational and Structural Biotechnology Journal, Vol 23, Iss , Pp 783-790 (2024)

    الوصف: Computational models of gene regulations help to understand regulatory mechanisms and are extensively used in a wide range of areas, e.g., biotechnology or medicine, with significant benefits. Unfortunately, there are only a few computational gene regulatory models of whole genomes allowing static and dynamic analysis due to the lack of sophisticated tools for their reconstruction. Here, we describe Augusta, an open-source Python package for Gene Regulatory Network (GRN) and Boolean Network (BN) inference from the high-throughput gene expression data. Augusta can reconstruct genome-wide models suitable for static and dynamic analyses. Augusta uses a unique approach where the first estimation of a GRN inferred from expression data is further refined by predicting transcription factor binding motifs in promoters of regulated genes and by incorporating verified interactions obtained from databases. Moreover, a refined GRN is transformed into a draft BN by searching in the curated model database and setting logical rules to incoming edges of target genes, which can be further manually edited as the model is provided in the SBML file format. The approach is applicable even if information about the organism under study is not available in the databases, which is typically the case for non-model organisms including most microbes. Augusta can be operated from the command line and, thus, is easy to use for automated prediction of models for various genomes. The Augusta package is freely available at github.com/JanaMus/Augusta. Documentation and tutorials are available at augusta.readthedocs.io.

    وصف الملف: electronic resource

  3. 3
    دورية أكاديمية
  4. 4
    دورية أكاديمية

    المصدر: Nature Communications, Vol 13, Iss 1, Pp 1-21 (2022)

    مصطلحات موضوعية: Science

    الوصف: Infection with SARS-COV-2 can result in self-limited upper airway infection or progress to a more systemic inflammatory condition including pneumonic COVID-19. Here the authors utilise a multi-omics approach to interrogate the immune response of patients with self-limiting upper respiratory SARS-CoV-2 infection and reveal a temporal immune trajectory they associate with viral containment and restriction from pneumonic progressive disease.

    وصف الملف: electronic resource

  5. 5
    دورية أكاديمية

    المصدر: Molecular Systems Biology, Vol 18, Iss 12, Pp n/a-n/a (2022)

    الوصف: Abstract Bacteria reorganize their physiology upon entry to stationary phase. What part of this reorganization improves starvation survival is a difficult question because the change in physiology includes a global reorganization of the proteome, envelope, and metabolism of the cell. In this work, we used several trade‐offs between fast growth and long survival to statistically score over 2,000 Escherichia coli proteins for their global correlation with death rate. The combined ranking allowed us to narrow down the set of proteins that positively correlate with survival and validate the causal role of a subset of proteins. Remarkably, we found that important survival genes are related to the cell envelope, i.e., periplasm and outer membrane, because the maintenance of envelope integrity of E. coli plays a crucial role during starvation. Our results uncover a new protective feature of the outer membrane that adds to the growing evidence that the outer membrane is not only a barrier that prevents abiotic substances from reaching the cytoplasm but also essential for bacterial proliferation and survival.

    وصف الملف: electronic resource

  6. 6
    دورية أكاديمية

    المصدر: Nature Communications, Vol 11, Iss 1, Pp 1-14 (2020)

    مصطلحات موضوعية: Science

    الوصف: Here, using computational integration of multi-omics data, the authors provide a detailed transcriptome and translatome of herpes simplex virus 1 (HSV-1), including previously unidentified ORFs and N-terminal extensions. The study also provides a HSV-1 genome browser and should be a valuable resource for further research.

    وصف الملف: electronic resource

  7. 7
    دورية أكاديمية

    المصدر: Computational and Structural Biotechnology Journal, Vol 18, Iss , Pp 1342-1351 (2020)

    الوصف: The MinION sequencer by Oxford Nanopore Technologies turns DNA and RNA sequencing into a routine task in biology laboratories or in field research. For downstream analysis it is required to have a sufficient amount of target reads. Especially prokaryotic or bacteriophagic sequencing samples can contain a significant amount of off-target sequences in the processed sample, stemming from human DNA/RNA contamination, insufficient rRNA depletion, or remaining DNA/RNA from other organisms (e.g. host organism from bacteriophage cultivation). Such impurity, contamination and off-targets (ICOs) block read capacity, requiring to sequence deeper. In comparison to second-generation sequencing, MinION sequencing allows to reuse its chip after a (partial) run. This allows further usage of the same chip with more sample, even after adjusting the library preparation to reduce ICOs. The earlier a sample’s ICOs are detected, the better the sequencing chip can be conserved for future use. Here we present sequ-into, a low-resource and user-friendly cross-platform tool to detect ICO sequences from a predefined ICO database in samples early during a MinION sequencing run. The data provided by sequ-into empowers the user to quickly take action to preserve sample material and chip capacity. sequ-into is available from https://github.com/mjoppich/sequ-intoTest

    وصف الملف: electronic resource

  8. 8
    دورية أكاديمية

    المصدر: Biotechnology for Biofuels, Vol 12, Iss 1, Pp 1-16 (2019)

    الوصف: Abstract Background One of the main obstacles preventing solventogenic clostridia from achieving higher yields in biofuel production is the toxicity of produced solvents. Unfortunately, regulatory mechanisms responsible for the shock response are poorly described on the transcriptomic level. Although the strain Clostridium beijerinckii NRRL B-598, a promising butanol producer, has been studied under different conditions in the past, its transcriptional response to a shock caused by butanol in the cultivation medium remains unknown. Results In this paper, we present a transcriptional response of the strain during a butanol challenge, caused by the addition of butanol to the cultivation medium at the very end of the acidogenic phase, using RNA-Seq. We resequenced and reassembled the genome sequence of the strain and prepared novel genome and gene ontology annotation to provide the most accurate results. When compared to samples under standard cultivation conditions, samples gathered during butanol shock represented a well-distinguished group. Using reference samples gathered directly before the addition of butanol, we identified genes that were differentially expressed in butanol challenge samples. We determined clusters of 293 down-regulated and 301 up-regulated genes whose expression was affected by the cultivation conditions. Enriched term “RNA binding” among down-regulated genes corresponded to the downturn of translation and the cluster contained a group of small acid-soluble spore proteins. This explained phenotype of the culture that had not sporulated. On the other hand, up-regulated genes were characterized by the term “protein binding” which corresponded to activation of heat-shock proteins that were identified within this cluster. Conclusions We provided an overall transcriptional response of the strain C. beijerinckii NRRL B-598 to butanol shock, supplemented by auxiliary technologies, including high-pressure liquid chromatography and flow cytometry, to capture the corresponding phenotypic response. We identified genes whose regulation was affected by the addition of butanol to the cultivation medium and inferred related molecular functions that were significantly influenced. Additionally, using high-quality genome assembly and custom-made gene ontology annotation, we demonstrated that this settled terminology, widely used for the analysis of model organisms, could also be applied to non-model organisms and for research in the field of biofuels.

    وصف الملف: electronic resource

  9. 9
    دورية أكاديمية
  10. 10
    دورية أكاديمية

    المصدر: JCI Insight, Vol 6, Iss 18 (2021)

    مصطلحات موضوعية: COVID-19, Vascular biology, Medicine

    الوصف: Neutrophils provide a critical line of defense in immune responses to various pathogens, inflicting self-damage upon transition to a hyperactivated, procoagulant state. Recent work has highlighted proinflammatory neutrophil phenotypes contributing to lung injury and acute respiratory distress syndrome (ARDS) in patients with coronavirus disease 2019 (COVID-19). Here, we use state-of-the art mass spectrometry–based proteomics and transcriptomic and correlative analyses as well as functional in vitro and in vivo studies to dissect how neutrophils contribute to the progression to severe COVID-19. We identify a reinforcing loop of both systemic and neutrophil intrinsic IL-8 (CXCL8/IL-8) dysregulation, which initiates and perpetuates neutrophil-driven immunopathology. This positive feedback loop of systemic and neutrophil autocrine IL-8 production leads to an activated, prothrombotic neutrophil phenotype characterized by degranulation and neutrophil extracellular trap (NET) formation. In severe COVID-19, neutrophils directly initiate the coagulation and complement cascade, highlighting a link to the immunothrombotic state observed in these patients. Targeting the IL-8–CXCR-1/-2 axis interferes with this vicious cycle and attenuates neutrophil activation, degranulation, NETosis, and IL-8 release. Finally, we show that blocking IL-8–like signaling reduces severe acute respiratory distress syndrome of coronavirus 2 (SARS-CoV-2) spike protein–induced, human ACE2–dependent pulmonary microthrombosis in mice. In summary, our data provide comprehensive insights into the activation mechanisms of neutrophils in COVID-19 and uncover a self-sustaining neutrophil–IL-8 axis as a promising therapeutic target in severe SARS-CoV-2 infection.

    وصف الملف: electronic resource