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  1. Article: How Chemotherapy Increases the Risk of Systemic Candidiasis in Cancer Patients: Current Paradigm and Future Directions.

    Teoh, Flora / Pavelka, Norman

    Pathogens (Basel, Switzerland)

    2016  Volume 5, Issue 1

    Abstract: Candida albicans is a fungal commensal and a major colonizer of the human skin, as well as of the gastrointestinal and genitourinary tracts. It is also one of the leading causes of opportunistic microbial infections in cancer patients, often presenting ... ...

    Abstract Candida albicans is a fungal commensal and a major colonizer of the human skin, as well as of the gastrointestinal and genitourinary tracts. It is also one of the leading causes of opportunistic microbial infections in cancer patients, often presenting in a life-threatening, systemic form. Increased susceptibility to such infections in cancer patients is attributed primarily to chemotherapy-induced depression of innate immune cells and weakened epithelial barriers, which are the body's first-line defenses against fungal infections. Moreover, classical chemotherapeutic agents also have a detrimental effect on components of the adaptive immune system, which further play important roles in the antifungal response. In this review, we discuss the current paradigm regarding the mechanisms behind the increased risk of systemic candidiasis in cancer patients. We also highlight some recent findings, which suggest that chemotherapy may have more extensive effects beyond the human host, in particular towards C. albicans itself and the bacterial microbiota. The extent to which these additional effects contribute towards the development of candidiasis in chemotherapy-treated patients remains to be investigated.
    Language English
    Publishing date 2016-01-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens5010006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The mammalian mycobiome: A complex system in a dynamic relationship with the host.

    Lai, Ghee Chuan / Tan, Tze Guan / Pavelka, Norman

    Wiley interdisciplinary reviews. Systems biology and medicine

    2018  Volume 11, Issue 1, Page(s) e1438

    Abstract: Mammalian barrier surfaces are densely populated by symbiont fungi in much the same way the former are colonized by symbiont bacteria. The fungal microbiota, otherwise known as the mycobiota, is increasingly recognized as a critical player in the ... ...

    Abstract Mammalian barrier surfaces are densely populated by symbiont fungi in much the same way the former are colonized by symbiont bacteria. The fungal microbiota, otherwise known as the mycobiota, is increasingly recognized as a critical player in the maintenance of health and homeostasis of the host. Here we discuss the impact of the mycobiota on host physiology and disease, the factors influencing mycobiota composition, and the current technologies used for identifying symbiont fungal species. Understanding the tripartite interactions among the host, mycobiota, and other members of the microbiota, will help to guide the development of novel prevention and therapeutic strategies for a variety of human diseases. This article is categorized under: Physiology > Mammalian Physiology in Health and Disease Laboratory Methods and Technologies > Genetic/Genomic Methods Models of Systems Properties and Processes > Organismal Models.
    MeSH term(s) Animals ; Bacteria/classification ; Bacteria/growth & development ; Fungi/classification ; Fungi/growth & development ; Humans ; Mycobiome/physiology
    Language English
    Publishing date 2018-09-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2503323-2
    ISSN 1939-005X ; 1939-5094
    ISSN (online) 1939-005X
    ISSN 1939-5094
    DOI 10.1002/wsbm.1438
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6790: Show issues Location:
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  3. Article ; Online: How Chemotherapy Increases the Risk of Systemic Candidiasis in Cancer Patients

    Flora Teoh / Norman Pavelka

    Pathogens, Vol 5, Iss 1, p

    Current Paradigm and Future Directions

    2016  Volume 6

    Abstract: Candida albicans is a fungal commensal and a major colonizer of the human skin, as well as of the gastrointestinal and genitourinary tracts. It is also one of the leading causes of opportunistic microbial infections in cancer patients, often presenting ... ...

    Abstract Candida albicans is a fungal commensal and a major colonizer of the human skin, as well as of the gastrointestinal and genitourinary tracts. It is also one of the leading causes of opportunistic microbial infections in cancer patients, often presenting in a life-threatening, systemic form. Increased susceptibility to such infections in cancer patients is attributed primarily to chemotherapy-induced depression of innate immune cells and weakened epithelial barriers, which are the body’s first-line defenses against fungal infections. Moreover, classical chemotherapeutic agents also have a detrimental effect on components of the adaptive immune system, which further play important roles in the antifungal response. In this review, we discuss the current paradigm regarding the mechanisms behind the increased risk of systemic candidiasis in cancer patients. We also highlight some recent findings, which suggest that chemotherapy may have more extensive effects beyond the human host, in particular towards C. albicans itself and the bacterial microbiota. The extent to which these additional effects contribute towards the development of candidiasis in chemotherapy-treated patients remains to be investigated.
    Keywords chemotherapy ; cancer ; Candida albicans ; immune system ; microbiota ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Emerging and evolving concepts in gene essentiality.

    Rancati, Giulia / Moffat, Jason / Typas, Athanasios / Pavelka, Norman

    Nature reviews. Genetics

    2017  Volume 19, Issue 1, Page(s) 34–49

    Abstract: Gene essentiality is a founding concept of genetics with important implications in both fundamental and applied research. Multiple screens have been performed over the years in bacteria, yeasts, animals and more recently in human cells to identify ... ...

    Abstract Gene essentiality is a founding concept of genetics with important implications in both fundamental and applied research. Multiple screens have been performed over the years in bacteria, yeasts, animals and more recently in human cells to identify essential genes. A mounting body of evidence suggests that gene essentiality, rather than being a static and binary property, is both context dependent and evolvable in all kingdoms of life. This concept of a non-absolute nature of gene essentiality changes our fundamental understanding of essential biological processes and could directly affect future treatment strategies for cancer and infectious diseases.
    MeSH term(s) Animals ; Conserved Sequence ; Drug Delivery Systems ; Drug Resistance/genetics ; Evolution, Molecular ; Gene Editing ; Gene Regulatory Networks ; Genes, Essential ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Metabolic Engineering ; Models, Genetic ; Synthetic Biology
    Language English
    Publishing date 2017-10-16
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2035157-4
    ISSN 1471-0064 ; 1471-0056
    ISSN (online) 1471-0064
    ISSN 1471-0056
    DOI 10.1038/nrg.2017.74
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5474: Show issues Location:
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  5. Article: The Elusive Anti-

    Tso, Gloria Hoi Wan / Reales-Calderon, Jose Antonio / Pavelka, Norman

    Frontiers in immunology

    2018  Volume 9, Page(s) 897

    Abstract: Candidemia is a bloodstream fungal infection caused ... ...

    Abstract Candidemia is a bloodstream fungal infection caused by
    MeSH term(s) Antifungal Agents/pharmacology ; Antifungal Agents/therapeutic use ; Candida/drug effects ; Candida/immunology ; Candidemia/drug therapy ; Candidemia/immunology ; Candidemia/microbiology ; Candidemia/prevention & control ; Candidiasis, Vulvovaginal/drug therapy ; Candidiasis, Vulvovaginal/immunology ; Candidiasis, Vulvovaginal/microbiology ; Candidiasis, Vulvovaginal/prevention & control ; Drug Resistance, Fungal/immunology ; Female ; Fungal Vaccines/immunology ; Fungal Vaccines/therapeutic use ; Humans ; Immunocompromised Host/immunology ; Opportunistic Infections/drug therapy ; Opportunistic Infections/immunology ; Opportunistic Infections/microbiology ; Opportunistic Infections/prevention & control ; Treatment Outcome
    Chemical Substances Antifungal Agents ; Fungal Vaccines
    Language English
    Publishing date 2018-04-27
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2018.00897
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  6. Article ; Online: Fungal Symbionts Produce Prostaglandin E

    Tan, Tze Guan / Lim, Ying Shiang / Tan, Alrina / Leong, Royston / Pavelka, Norman

    Frontiers in cellular and infection microbiology

    2019  Volume 9, Page(s) 359

    Abstract: ... Candida ... ...

    Abstract Candida albicans
    MeSH term(s) Animals ; Candida albicans/physiology ; Dinoprostone/metabolism ; Fungi/physiology ; Host-Pathogen Interactions ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/microbiology ; Macrophages/metabolism ; Mice ; Mice, Knockout ; Mutation ; Phagocytes/metabolism ; Symbiosis ; Virulence/genetics
    Chemical Substances Dinoprostone (K7Q1JQR04M)
    Language English
    Publishing date 2019-10-18
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2019.00359
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Karyotypic changes as drivers and catalyzers of cellular evolvability: a perspective from non-pathogenic yeasts.

    Rancati, Giulia / Pavelka, Norman

    Seminars in cell & developmental biology

    2013  Volume 24, Issue 4, Page(s) 332–338

    Abstract: In spite of the existence of multiple cellular mechanisms that ensure genome stability, thanks to the advent of quantitative genomic assays in the last decade, an unforeseen level of plasticity in cellular genomes has begun to emerge in many different ... ...

    Abstract In spite of the existence of multiple cellular mechanisms that ensure genome stability, thanks to the advent of quantitative genomic assays in the last decade, an unforeseen level of plasticity in cellular genomes has begun to emerge in many different fields of cell biology. Eukaryotic cells not only have a remarkable ability to change their karyotypes in response to various perturbations, but also these karyotypic changes impact cellular fitness and in some circumstances enable evolutionary adaptation. In this review, we focus on recent findings in non-pathogenic yeasts indicating that karyotypic changes generate selectable phenotypic variation and alter genomic instability. Based on these findings, we propose that in highly stressful and thus strongly selective environments karyotypic changes could act both as a driver and as a catalyzer of cellular adaptation, i.e. karyotypic changes drive large phenotypic leaps and at the same time catalyze the accumulation of even more genotypic and karyotypic changes.
    MeSH term(s) Aneuploidy ; Biological Evolution ; Genomic Instability ; Karyotyping ; Polyploidy ; Yeasts/genetics
    Language English
    Publishing date 2013-04
    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.2013.01.009
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2918: Show issues Location:
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  8. Article ; Online: Aneuploidy Enables Cross-Adaptation to Unrelated Drugs.

    Yang, Feng / Teoh, Flora / Tan, Alrina Shin Min / Cao, Yongbing / Pavelka, Norman / Berman, Judith

    Molecular biology and evolution

    2019  Volume 36, Issue 8, Page(s) 1768–1782

    Abstract: Aneuploidy is common both in tumor cells responding to chemotherapeutic agents and in fungal cells adapting to antifungal drugs. Because aneuploidy simultaneously affects many genes, it has the potential to confer multiple phenotypes to the same cells. ... ...

    Abstract Aneuploidy is common both in tumor cells responding to chemotherapeutic agents and in fungal cells adapting to antifungal drugs. Because aneuploidy simultaneously affects many genes, it has the potential to confer multiple phenotypes to the same cells. Here, we analyzed the mechanisms by which Candida albicans, the most prevalent human fungal pathogen, acquires the ability to survive both chemotherapeutic agents and antifungal drugs. Strikingly, adaptation to both types of drugs was accompanied by the acquisition of specific whole-chromosome aneuploidies, with some aneuploid karyotypes recovered independently and repeatedly from very different drug conditions. Specifically, strains selected for survival in hydroxyurea, an anticancer drug, acquired cross-adaptation to caspofungin, a first-line antifungal drug, and both acquired traits were attributable to trisomy of the same chromosome: loss of trisomy was accompanied by loss of adaptation to both drugs. Mechanistically, aneuploidy simultaneously altered the copy number of most genes on chromosome 2, yet survival in hydroxyurea or caspofungin required different genes and stress response pathways. Similarly, chromosome 5 monosomy conferred increased tolerance to both fluconazole and to caspofungin, antifungals with different mechanisms of action. Thus, the potential for cross-adaptation is not a feature of aneuploidy per se; rather, it is dependent on specific genes harbored on given aneuploid chromosomes. Furthermore, pre-exposure to hydroxyurea increased the frequency of appearance of caspofungin survivors, and hydroxyurea-adapted C. albicans cells were refractory to antifungal drug treatment in a mouse model of systemic candidiasis. This highlights the potential clinical consequences for the management of cancer chemotherapy patients at risk of fungal infections.
    MeSH term(s) Adaptation, Biological ; Aneuploidy ; Animals ; Antifungal Agents ; Antineoplastic Agents ; Calcineurin ; Candida albicans/genetics ; Caspofungin ; Chromosomes, Fungal ; Drug Resistance, Fungal/genetics ; Hydroxyurea ; Mice
    Chemical Substances Antifungal Agents ; Antineoplastic Agents ; Calcineurin (EC 3.1.3.16) ; Caspofungin (F0XDI6ZL63) ; Hydroxyurea (X6Q56QN5QC)
    Language English
    Publishing date 2019-05-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 998579-7
    ISSN 1537-1719 ; 0737-4038
    ISSN (online) 1537-1719
    ISSN 0737-4038
    DOI 10.1093/molbev/msz104
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2137: Show issues Location:
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  9. Article ; Online: Gut-Evolved

    Reales-Calderon, Jose Antonio / Tso, Gloria H W / Tan, Alrina S M / Hor, Pei Xiang / Böhme, Julia / Teng, Karen W W / Newell, Evan W / Singhal, Amit / Pavelka, Norman

    Frontiers in cellular and infection microbiology

    2021  Volume 11, Page(s) 743735

    Abstract: Serial passaging of the human fungal ... ...

    Abstract Serial passaging of the human fungal pathogen
    MeSH term(s) Animals ; Candida albicans ; Cell Wall ; Macrophages ; Mice ; Neutrophils ; beta-Glucans
    Chemical Substances beta-Glucans
    Language English
    Publishing date 2021-11-22
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2021.743735
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  10. Article ; Online: When one and one gives more than two: challenges and opportunities of integrative omics.

    Choi, Hyungwon / Pavelka, Norman

    Frontiers in genetics

    2012  Volume 2, Page(s) 105

    Abstract: Since the dawn of the post-genomic era a myriad of novel high-throughput technologies have been developed that are capable of measuring thousands of biological molecules at once, giving rise to various "omics" platforms. These advances offer the unique ... ...

    Abstract Since the dawn of the post-genomic era a myriad of novel high-throughput technologies have been developed that are capable of measuring thousands of biological molecules at once, giving rise to various "omics" platforms. These advances offer the unique opportunity to study how individual parts of a biological system work together to produce emerging phenotypes. Today, many research laboratories are moving toward applying multiple omics platforms to analyze the same biological samples. In addition, network information of interacting molecules is being incorporated more and more into the analysis and interpretation of these multiple omics datasets, which provides novel ways to integrate multiple layers of heterogeneous biological information into a single coherent picture. Here, we provide a perspective on how such recent "integrative omics" efforts are likely going to shift biological paradigms once again, and what challenges lie ahead.
    Language English
    Publishing date 2012-01-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606823-0
    ISSN 1664-8021 ; 1664-8021
    ISSN (online) 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2011.00105
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