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  1. Article ; Online: huva: A human variation analysis framework to predict gene perturbation from population-scale multi-omics data.

    Aschenbrenner, Anna C / Bonaguro, Lorenzo

    STAR protocols

    2023  Volume 4, Issue 2, Page(s) 102193

    Abstract: Variance of gene expression is intrinsic to any given natural population. Here, we present a protocol to analyze this variance using a conditional quasi loss- and gain-of-function approach. The huva (human variation) package takes advantage of population- ...

    Abstract Variance of gene expression is intrinsic to any given natural population. Here, we present a protocol to analyze this variance using a conditional quasi loss- and gain-of-function approach. The huva (human variation) package takes advantage of population-scale multi-omics data to infer gene function and the relationship between phenotype and gene expression. We describe the steps for setting up the huva workspace, formatting datasets, performing huva experiments, and exporting data. For complete details on the use and execution of this protocol, please refer to Bonaguro et al. (2022).
    Language English
    Publishing date 2023-03-24
    Publishing country United States
    Document type Journal Article
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2023.102193
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: huva

    Anna C. Aschenbrenner / Lorenzo Bonaguro

    STAR Protocols, Vol 4, Iss 2, Pp 102193- (2023)

    A human variation analysis framework to predict gene perturbation from population-scale multi-omics data

    2023  

    Abstract: Summary: Variance of gene expression is intrinsic to any given natural population. Here, we present a protocol to analyze this variance using a conditional quasi loss- and gain-of-function approach. The huva (human variation) package takes advantage of ... ...

    Abstract Summary: Variance of gene expression is intrinsic to any given natural population. Here, we present a protocol to analyze this variance using a conditional quasi loss- and gain-of-function approach. The huva (human variation) package takes advantage of population-scale multi-omics data to infer gene function and the relationship between phenotype and gene expression. We describe the steps for setting up the huva workspace, formatting datasets, performing huva experiments, and exporting data.For complete details on the use and execution of this protocol, please refer to Bonaguro et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
    Keywords Bioinformatics ; RNAseq ; Immunology ; Gene Expression ; Systems Biology ; Science (General) ; Q1-390
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: [No title information]

    Ulas, Thomas / Aschenbrenner, Anna C

    Biospektrum : Zeitschrift der Gesellschaft fur Biologishe Chemie (GBCH) und der Vereinigung fur Allgemeine und Angewandte Mikrobiologie (VAAM)

    2021  Volume 27, Issue 4, Page(s) 372–375

    Abstract: The COVID-19 pandemic is leading to increasing numbers of patients all over the world. Reports on a dysregulated immune system in the severe cases calls for a better characterization of the ongoing changes. To dissect COVID-19-driven immune host ... ...

    Title translation Neue Krankheiten mit Bluttranskriptomik entschlüsseln.
    Abstract The COVID-19 pandemic is leading to increasing numbers of patients all over the world. Reports on a dysregulated immune system in the severe cases calls for a better characterization of the ongoing changes. To dissect COVID-19-driven immune host responses, we profiled whole blood transcriptomes enabling a data-driven stratification based on molecular phenotype. This analysis allowed prediction of patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host.
    Language German
    Publishing date 2021-06-26
    Publishing country Germany
    Document type English Abstract ; Journal Article ; Review
    ZDB-ID 2203536-9
    ISSN 1868-6249 ; 0947-0867
    ISSN (online) 1868-6249
    ISSN 0947-0867
    DOI 10.1007/s12268-021-1590-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: COVID-19 and the human innate immune system.

    Schultze, Joachim L / Aschenbrenner, Anna C

    Cell

    2021  Volume 184, Issue 7, Page(s) 1671–1692

    Abstract: The introduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the human population represents a tremendous medical and economic crisis. Innate immunity-as the first line of defense of our immune system-plays a central role in ... ...

    Abstract The introduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the human population represents a tremendous medical and economic crisis. Innate immunity-as the first line of defense of our immune system-plays a central role in combating this novel virus. Here, we provide a conceptual framework for the interaction of the human innate immune system with SARS-CoV-2 to link the clinical observations with experimental findings that have been made during the first year of the pandemic. We review evidence that variability in innate immune system components among humans is a main contributor to the heterogeneous disease courses observed for coronavirus disease 2019 (COVID-19), the disease spectrum induced by SARS-CoV-2. A better understanding of the pathophysiological mechanisms observed for cells and soluble mediators involved in innate immunity is a prerequisite for the development of diagnostic markers and therapeutic strategies targeting COVID-19. However, this will also require additional studies addressing causality of events, which so far are lagging behind.
    MeSH term(s) COVID-19/immunology ; Host Microbial Interactions ; Humans ; Immunity, Innate ; SARS-CoV-2/physiology ; Severity of Illness Index
    Language English
    Publishing date 2021-02-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2021.02.029
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Whole blood stimulation as a tool for studying the human immune system.

    Müller, Sophie / Kröger, Charlotte / Schultze, Joachim L / Aschenbrenner, Anna C

    European journal of immunology

    2023  Volume 54, Issue 2, Page(s) e2350519

    Abstract: The human immune system is best accessible via tissues and organs not requiring major surgical intervention, such as blood. In many circumstances, circulating immune cells correlate with an individual's health state and give insight into physiological ... ...

    Abstract The human immune system is best accessible via tissues and organs not requiring major surgical intervention, such as blood. In many circumstances, circulating immune cells correlate with an individual's health state and give insight into physiological and pathophysiological processes. Stimulating whole blood ex vivo is a powerful tool to investigate immune responses. In the context of clinical research, the applications of whole blood stimulation include host immunity, disease characterization, diagnosis, treatment, and drug development. Here, we summarize different setups and readouts of whole blood assays and discuss applications for preclinical research and clinical practice. Finally, we propose combining whole blood stimulation with high-throughput technologies, such as single-cell RNA-sequencing, to comprehensively analyze the human immune system for the identification of biomarkers, therapeutic interventions as well as companion diagnostics.
    MeSH term(s) Humans ; Immune System ; Blood
    Language English
    Publishing date 2023-12-16
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.202350519
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Systems immunology allows a new view on human dendritic cells.

    Schultze, Joachim L / Aschenbrenner, Anna C

    Seminars in cell & developmental biology

    2018  Volume 86, Page(s) 15–23

    Abstract: As the most important antigen-presenting cells, dendritic cells connect the innate and adaptive part of our immune system and play a pivotal role in our course of action against invading pathogens as well as during successful vaccination. Immunologists ... ...

    Abstract As the most important antigen-presenting cells, dendritic cells connect the innate and adaptive part of our immune system and play a pivotal role in our course of action against invading pathogens as well as during successful vaccination. Immunologists have therefore studied these cells in great detail using flow cytometry-based analyses, in vitro assays and in vivo models, both in murine models and in humans. Albeit, sophisticated, classical immunological, and molecular approaches were often unable to unequivocally determine the subpopulation structure of the dendritic cell lineage and not surprisingly, conflicting results about dendritic cell subsets co-existed throughout the last decades. With the advent of systems approaches and the most recent introduction of -omics approaches on the single cell level combined with multi-colour flow cytometry or mass cytometry, we now enter an era allowing us to define cell population structures with an unprecedented precision. We will report here on the most recent studies applying these technologies to human dendritic cells. Proper delineation of and definition of molecular signatures for the different human dendritic cell subsets will greatly facilitate studying these cells in the future: understanding their function under physiological as well as pathological conditions.
    MeSH term(s) Animals ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Humans ; Immune System/cytology ; Immune System/immunology ; Single-Cell Analysis ; Systems Biology
    Language English
    Publishing date 2018-02-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1312473-0
    ISSN 1096-3634 ; 1084-9521
    ISSN (online) 1096-3634
    ISSN 1084-9521
    DOI 10.1016/j.semcdb.2018.02.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: A guide to systems-level immunomics.

    Bonaguro, Lorenzo / Schulte-Schrepping, Jonas / Ulas, Thomas / Aschenbrenner, Anna C / Beyer, Marc / Schultze, Joachim L

    Nature immunology

    2022  Volume 23, Issue 10, Page(s) 1412–1423

    Abstract: The immune system is highly complex and distributed throughout an organism, with hundreds to thousands of cell states existing in parallel with diverse molecular pathways interacting in a highly dynamic and coordinated fashion. Although the ... ...

    Abstract The immune system is highly complex and distributed throughout an organism, with hundreds to thousands of cell states existing in parallel with diverse molecular pathways interacting in a highly dynamic and coordinated fashion. Although the characterization of individual genes and molecules is of the utmost importance for understanding immune-system function, high-throughput, high-resolution omics technologies combined with sophisticated computational modeling and machine-learning approaches are creating opportunities to complement standard immunological methods with new insights into immune-system dynamics. Like systems immunology itself, immunology researchers must take advantage of these technologies and form their own diverse networks, connecting with researchers from other disciplines. This Review is an introduction and 'how-to guide' for immunologists with no particular experience in the field of omics but with the intention to learn about and apply these systems-level approaches, and for immunologists who want to make the most of interdisciplinary networks.
    MeSH term(s) Computer Simulation ; Immune System ; Machine Learning
    Language English
    Publishing date 2022-09-22
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-022-01309-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: New "programmers" in tissue macrophage activation.

    Aschenbrenner, Anna C / Schultze, Joachim L

    Pflugers Archiv : European journal of physiology

    2017  Volume 469, Issue 3-4, Page(s) 375–383

    Abstract: Tissue macrophages and monocyte-derived macrophages are under continuous influence from environmental signals that define their activation status. Along these lines, macrophages integrate tissue and stress signals and are specifically programmed by these ...

    Abstract Tissue macrophages and monocyte-derived macrophages are under continuous influence from environmental signals that define their activation status. Along these lines, macrophages integrate tissue and stress signals and are specifically programmed by these signals towards a spectrum of functions necessary to fulfill their duty within their particular microenvironment, be it homeostatic tissue function, response to inflammatory pathophysiology, or even resolution of an inflammation. Recent years have seen tremendous progress in our understanding how macrophages at different sites are transcriptionally and epigenetically programmed to execute their diverse tasks throughout the body. The identification of transcription factors guiding these reprogramming activities is currently a major topic in macrophage research. We summarize the most recent findings within the last 18 months concerning the identification of novel transcription factors associated with particular macrophage location or function. Furthermore, we extend the view of cellular programming of macrophages to additional levels of regulation, for example, by long non-coding RNAs. Clearly, in addition to transcription factors, there are many more "programmers" shaping the versatile functionality of these exciting innate immune cells.
    MeSH term(s) Animals ; Homeostasis/physiology ; Humans ; Inflammation/metabolism ; Inflammation/pathology ; Macrophage Activation/physiology ; Macrophages/metabolism ; Macrophages/physiology ; Transcription Factors/metabolism
    Chemical Substances Transcription Factors
    Language English
    Publishing date 2017-02-09
    Publishing country Germany
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 6380-0
    ISSN 1432-2013 ; 0031-6768
    ISSN (online) 1432-2013
    ISSN 0031-6768
    DOI 10.1007/s00424-017-1943-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Epigenetic reprogramming of immune cells in injury, repair, and resolution.

    Placek, Katarzyna / Schultze, Joachim L / Aschenbrenner, Anna C

    The Journal of clinical investigation

    2019  Volume 129, Issue 8, Page(s) 2994–3005

    Abstract: Immune cells are pivotal in the reaction to injury, whereupon, under ideal conditions, repair and resolution phases restore homeostasis following initial acute inflammation. Immune cell activation and reprogramming require transcriptional changes that ... ...

    Abstract Immune cells are pivotal in the reaction to injury, whereupon, under ideal conditions, repair and resolution phases restore homeostasis following initial acute inflammation. Immune cell activation and reprogramming require transcriptional changes that can only be initiated if epigenetic alterations occur. Recently, accelerated deciphering of epigenetic mechanisms has extended knowledge of epigenetic regulation, including long-distance chromatin remodeling, DNA methylation, posttranslational histone modifications, and involvement of small and long noncoding RNAs. Epigenetic changes have been linked to aspects of immune cell development, activation, and differentiation. Furthermore, genome-wide epigenetic landscapes have been established for some immune cells, including tissue-resident macrophages, and blood-derived cells including T cells. The epigenetic mechanisms underlying developmental steps from hematopoietic stem cells to fully differentiated immune cells led to development of epigenetic technologies and insights into general rules of epigenetic regulation. Compared with more advanced research areas, epigenetic reprogramming of immune cells in injury remains in its infancy. While the early epigenetic mechanisms supporting activation of the immune response to injury have been studied, less is known about resolution and repair phases and cell type-specific changes. We review prominent recent findings concerning injury-mediated epigenetic reprogramming, particularly in stroke and myocardial infarction. Lastly, we illustrate how single-cell technologies will be crucial to understanding epigenetic reprogramming in the complex sequential processes following injury.
    MeSH term(s) Animals ; Cellular Reprogramming/immunology ; DNA Methylation/immunology ; Epigenesis, Genetic/immunology ; Histones/immunology ; Humans ; Myocardial Infarction/immunology ; Myocardial Infarction/pathology ; Protein Processing, Post-Translational/immunology ; Stroke/immunology ; Stroke/pathology
    Chemical Substances Histones
    Language English
    Publishing date 2019-07-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI124619
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Effects of Unilateral Conditioning Activity on Acute Performance Enhancement: A Systematic Review.

    Krzysztofik, Michał / Wilk, Michał / Pisz, Anna / Kolinger, Dominik / Tsoukos, Athanasios / Aschenbrenner, Piotr / Stastny, Petr / Bogdanis, Gregory C

    Journal of sports science & medicine

    2022  Volume 21, Issue 4, Page(s) 625–639

    Abstract: This review aimed to summarize the reported effects of unilateral conditioning activity (CA) on unilateral performance, bilateral performance, and the contribution of activated body limb to bilateral performance. A systematic search on MEDLINE, ... ...

    Abstract This review aimed to summarize the reported effects of unilateral conditioning activity (CA) on unilateral performance, bilateral performance, and the contribution of activated body limb to bilateral performance. A systematic search on MEDLINE, SPORTDiscus, Scopus, and Google Scholar was conducted on February 2022. Twenty-three studies met the inclusion criteria. Throwing, jumping, swimming, change of direction, and isokinetic performance were used as outcome measures to assess the impact of unilateral CAs on inducing post-activation performance enhancement. Eleven studies examined the effectiveness of resistance exercises as a CA, seven investigated plyometric exercises, and five used isokinetic muscle actions as CAs. Notably, only three studies directly compared the effects of bilateral and unilateral CA, and no study reported possible changes in the contribution of each limb during bilateral exercises executed following unilateral CA. Split squats were the most often studied CA (7), and it was shown that multiple sets of high-loaded split squats (85% one-repetition maximum) executed as CA, improve vertical jumping and change of direction after 4 to 8 min of recovery. At the same time, multiple sets of alternate leg bounds performed with ~10% body weight or without any external load result in an improvement of sprint performance, 2 and 8 min later, with the effect being greater when loaded jumps are used. The unilateral CAs such as split squats, alternate leg bounds, and drop jumps can be effectively used to acutely improve a wide variety of athletic tasks, including jumping, sprinting, change of direction, and swimming performance.
    Language English
    Publishing date 2022-12-01
    Publishing country Turkey
    Document type Journal Article ; Review
    ZDB-ID 2075564-8
    ISSN 1303-2968 ; 1303-2968
    ISSN (online) 1303-2968
    ISSN 1303-2968
    DOI 10.52082/jssm.2022.625
    Database MEDical Literature Analysis and Retrieval System OnLINE

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