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  1. Article ; Online: StellarPath: Hierarchical-vertical multi-omics classifier synergizes stable markers and interpretable similarity networks for patient profiling.

    Giudice, Luca / Mohamed, Ahmed / Malm, Tarja

    PLoS computational biology

    2024  Volume 20, Issue 4, Page(s) e1012022

    Abstract: The Patient Similarity Network paradigm implies modeling the similarity between patients based on specific data. The similarity can summarize patients' relationships from high-dimensional data, such as biological omics. The end PSN can undergo un/ ... ...

    Abstract The Patient Similarity Network paradigm implies modeling the similarity between patients based on specific data. The similarity can summarize patients' relationships from high-dimensional data, such as biological omics. The end PSN can undergo un/supervised learning tasks while being strongly interpretable, tailored for precision medicine, and ready to be analyzed with graph-theory methods. However, these benefits are not guaranteed and depend on the granularity of the summarized data, the clarity of the similarity measure, the complexity of the network's topology, and the implemented methods for analysis. To date, no patient classifier fully leverages the paradigm's inherent benefits. PSNs remain complex, unexploited, and meaningless. We present StellarPath, a hierarchical-vertical patient classifier that leverages pathway analysis and patient similarity concepts to find meaningful features for both classes and individuals. StellarPath processes omics data, hierarchically integrates them into pathways, and uses a novel similarity to measure how patients' pathway activity is alike. It selects biologically relevant molecules, pathways, and networks, considering molecule stability and topology. A graph convolutional neural network then predicts unknown patients based on known cases. StellarPath excels in classification performances and computational resources across sixteen datasets. It demonstrates proficiency in inferring the class of new patients described in external independent studies, following its initial training and testing phases on a local dataset. It advances the PSN paradigm and provides new markers, insights, and tools for in-depth patient profiling.
    MeSH term(s) Humans ; Computational Biology/methods ; Precision Medicine/methods ; Neural Networks, Computer ; Algorithms ; Genomics/methods ; Biomarkers/metabolism ; Gene Expression Profiling/methods ; Proteomics/methods ; Multiomics
    Chemical Substances Biomarkers
    Language English
    Publishing date 2024-04-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1012022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Glia-Derived Extracellular Vesicles: Role in Central Nervous System Communication in Health and Disease.

    Pistono, Cristiana / Bister, Nea / Stanová, Iveta / Malm, Tarja

    Frontiers in cell and developmental biology

    2021  Volume 8, Page(s) 623771

    Abstract: Glial cells are crucial for the maintenance of correct neuronal functionality in a physiological state and intervene to restore the equilibrium when environmental or pathological conditions challenge central nervous system homeostasis. The communication ... ...

    Abstract Glial cells are crucial for the maintenance of correct neuronal functionality in a physiological state and intervene to restore the equilibrium when environmental or pathological conditions challenge central nervous system homeostasis. The communication between glial cells and neurons is essential and extracellular vesicles (EVs) take part in this function by transporting a plethora of molecules with the capacity to influence the function of the recipient cells. EVs, including exosomes and microvesicles, are a heterogeneous group of biogenetically distinct double membrane-enclosed vesicles. Once released from the cell, these two types of vesicles are difficult to discern, thus we will call them with the general term of EVs. This review is focused on the EVs secreted by astrocytes, oligodendrocytes and microglia, aiming to shed light on their influence on neurons and on the overall homeostasis of the central nervous system functions. We collect evidence on neuroprotective and homeostatic effects of glial EVs, including neuronal plasticity. On the other hand, current knowledge of the detrimental effects of the EVs in pathological conditions is addressed. Finally, we propose directions for future studies and we evaluate the potential of EVs as a therapeutic treatment for neurological disorders.
    Language English
    Publishing date 2021-01-25
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2020.623771
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Editorial: Air pollution and brain health.

    White, Anthony / Kanninen, Katja / Malm, Tarja / Schins, Roel

    Neurochemistry international

    2020  Volume 141, Page(s) 104900

    MeSH term(s) Air Pollution/adverse effects ; Animals ; Brain/physiology ; Environmental Exposure ; Humans ; Particulate Matter
    Chemical Substances Particulate Matter
    Language English
    Publishing date 2020-11-07
    Publishing country England
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 283190-9
    ISSN 1872-9754 ; 0197-0186
    ISSN (online) 1872-9754
    ISSN 0197-0186
    DOI 10.1016/j.neuint.2020.104900
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Glia-Derived Extracellular Vesicles

    Cristiana Pistono / Nea Bister / Iveta Stanová / Tarja Malm

    Frontiers in Cell and Developmental Biology, Vol

    Role in Central Nervous System Communication in Health and Disease

    2021  Volume 8

    Abstract: Glial cells are crucial for the maintenance of correct neuronal functionality in a physiological state and intervene to restore the equilibrium when environmental or pathological conditions challenge central nervous system homeostasis. The communication ... ...

    Abstract Glial cells are crucial for the maintenance of correct neuronal functionality in a physiological state and intervene to restore the equilibrium when environmental or pathological conditions challenge central nervous system homeostasis. The communication between glial cells and neurons is essential and extracellular vesicles (EVs) take part in this function by transporting a plethora of molecules with the capacity to influence the function of the recipient cells. EVs, including exosomes and microvesicles, are a heterogeneous group of biogenetically distinct double membrane-enclosed vesicles. Once released from the cell, these two types of vesicles are difficult to discern, thus we will call them with the general term of EVs. This review is focused on the EVs secreted by astrocytes, oligodendrocytes and microglia, aiming to shed light on their influence on neurons and on the overall homeostasis of the central nervous system functions. We collect evidence on neuroprotective and homeostatic effects of glial EVs, including neuronal plasticity. On the other hand, current knowledge of the detrimental effects of the EVs in pathological conditions is addressed. Finally, we propose directions for future studies and we evaluate the potential of EVs as a therapeutic treatment for neurological disorders.
    Keywords extracellular vesicle ; glia ; central nervous system ; astrocyte ; oligodendrocytes ; microglia ; Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Mechanisms Leading to Increased Insulin-Stimulated Cerebral Glucose Uptake in Obesity and Insulin Resistance: A High-Fat Diet and Exercise Training Intervention PET Study with Rats (CROSRAT).

    Jalo, Anna / Helin, Jatta S / Hentilä, Jaakko / Nissinen, Tuuli A / Honkala, Sanna M / Heiskanen, Marja A / Löyttyniemi, Eliisa / Malm, Tarja / Hannukainen, Jarna C

    Journal of functional morphology and kinesiology

    2024  Volume 9, Issue 2

    Abstract: Recent studies have shown that obesity and insulin resistance are associated with increased insulin-stimulated glucose uptake (GU) in the brain. Thus, insulin sensitivity seems to work differently in the brain compared to the peripheral tissues like ... ...

    Abstract Recent studies have shown that obesity and insulin resistance are associated with increased insulin-stimulated glucose uptake (GU) in the brain. Thus, insulin sensitivity seems to work differently in the brain compared to the peripheral tissues like skeletal muscles, but the underlying mechanisms remain unknown. Regular exercise training improves skeletal muscle and whole-body insulin sensitivity. However, the effect of exercise on glucose metabolism in the brain and internal organs is less well understood. The CROSRAT study aims to investigate the effects of exercise training on brain glucose metabolism and inflammation in a high-fat diet-induced rat model of obesity and insulin resistance. Male Sprague Dawley rats (
    Language English
    Publishing date 2024-03-25
    Publishing country Switzerland
    Document type Journal Article
    ISSN 2411-5142
    ISSN (online) 2411-5142
    DOI 10.3390/jfmk9020058
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The State of the Art of Piezo1 Channels in Skeletal Muscle Regeneration.

    Bernareggi, Annalisa / Bosutti, Alessandra / Massaria, Gabriele / Giniatullin, Rashid / Malm, Tarja / Sciancalepore, Marina / Lorenzon, Paola

    International journal of molecular sciences

    2022  Volume 23, Issue 12

    Abstract: Piezo1 channels are highly mechanically-activated cation channels that can sense and transduce the mechanical stimuli into physiological signals in different tissues including skeletal muscle. In this focused review, we summarize the emerging evidence of ...

    Abstract Piezo1 channels are highly mechanically-activated cation channels that can sense and transduce the mechanical stimuli into physiological signals in different tissues including skeletal muscle. In this focused review, we summarize the emerging evidence of Piezo1 channel-mediated effects in the physiology of skeletal muscle, with a particular focus on the role of Piezo1 in controlling myogenic precursor activity and skeletal muscle regeneration and vascularization. The disclosed effects reported by pharmacological activation of Piezo1 channels with the selective agonist Yoda1 indicate a potential impact of Piezo1 channel activity in skeletal muscle regeneration, which is disrupted in various muscular pathological states. All findings reported so far agree with the idea that Piezo1 channels represent a novel, powerful molecular target to develop new therapeutic strategies for preventing or ameliorating skeletal muscle disorders characterized by an impairment of tissue regenerative potential.
    MeSH term(s) Biological Transport ; Ion Channels/metabolism ; Mechanotransduction, Cellular/physiology ; Muscle Development ; Muscle, Skeletal/metabolism
    Chemical Substances Ion Channels
    Language English
    Publishing date 2022-06-14
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23126616
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Microglia Development and Maturation and Its Implications for Induction of Microglia-Like Cells from Human iPSCs.

    Wurm, Johannes / Konttinen, Henna / Andressen, Christian / Malm, Tarja / Spittau, Björn

    International journal of molecular sciences

    2021  Volume 22, Issue 6

    Abstract: Microglia are resident immune cells of the central nervous system and play critical roles during the development, homeostasis, and pathologies of the brain. Originated from yolk sac erythromyeloid progenitors, microglia immigrate into the embryonic brain ...

    Abstract Microglia are resident immune cells of the central nervous system and play critical roles during the development, homeostasis, and pathologies of the brain. Originated from yolk sac erythromyeloid progenitors, microglia immigrate into the embryonic brain parenchyma to undergo final postnatal differentiation and maturation driven by distinct chemokines, cytokines, and growth factors. Among them, TGFβ1 is an important regulator of microglial functions, mediating homeostasis, anti-inflammation, and triggering the expression of microglial homeostatic signature genes. Since microglia studies are mainly based on rodent cells and the isolation of homeostatic microglia from human tissue is challenging, human-induced pluripotent stem cells have been successfully differentiated into microglia-like cells recently. However, employed differentiation protocols strongly vary regarding used cytokines and growth factors, culture conditions, time span, and cell yield. Moreover, the incomplete differentiation of human microglia can hamper the similarity to primary human microglia and dramatically influence the outcome of follow-up studies with these differentiated cells. This review summarizes the current knowledge of the molecular mechanisms driving rodent microglia differentiation in vivo, further compares published differentiation protocols, and highlights the potential of TGFβ as an essential maturation factor.
    MeSH term(s) Animals ; Cell Differentiation ; Cell-Matrix Junctions/metabolism ; Humans ; Induced Pluripotent Stem Cells/cytology ; Microglia/cytology ; Microglia/metabolism ; Models, Biological ; Transforming Growth Factor beta/metabolism
    Chemical Substances Transforming Growth Factor beta
    Language English
    Publishing date 2021-03-17
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22063088
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Particulate matter from car exhaust alters function of human iPSC-derived microglia.

    Jäntti, Henna / Jonk, Steffi / Gómez Budia, Mireia / Ohtonen, Sohvi / Fagerlund, Ilkka / Fazaludeen, Mohammad Feroze / Aakko-Saksa, Päivi / Pebay, Alice / Lehtonen, Šárka / Koistinaho, Jari / Kanninen, Katja M / Jalava, Pasi I / Malm, Tarja / Korhonen, Paula

    Particle and fibre toxicology

    2024  Volume 21, Issue 1, Page(s) 6

    Abstract: Background: Air pollution is recognized as an emerging environmental risk factor for neurological diseases. Large-scale epidemiological studies associate traffic-related particulate matter (PM) with impaired cognitive functions and increased incidence ... ...

    Abstract Background: Air pollution is recognized as an emerging environmental risk factor for neurological diseases. Large-scale epidemiological studies associate traffic-related particulate matter (PM) with impaired cognitive functions and increased incidence of neurodegenerative diseases such as Alzheimer's disease. Inhaled components of PM may directly invade the brain via the olfactory route, or act through peripheral system responses resulting in inflammation and oxidative stress in the brain. Microglia are the immune cells of the brain implicated in the progression of neurodegenerative diseases. However, it remains unknown how PM affects live human microglia.
    Results: Here we show that two different PMs derived from exhausts of cars running on EN590 diesel or compressed natural gas (CNG) alter the function of human microglia-like cells in vitro. We exposed human induced pluripotent stem cell (iPSC)-derived microglia-like cells (iMGLs) to traffic related PMs and explored their functional responses. Lower concentrations of PMs ranging between 10 and 100 µg ml
    Conclusions: Our study indicates that traffic-related air pollutants alter the function of human microglia and warrant further studies to determine whether these changes contribute to adverse effects in the brain and on cognition over time. This study demonstrates human iPSC-microglia as a valuable tool to study functional microglial responses to environmental agents.
    MeSH term(s) Humans ; Particulate Matter/toxicity ; Particulate Matter/analysis ; Microglia/chemistry ; Induced Pluripotent Stem Cells/chemistry ; Automobiles ; Reactive Oxygen Species ; Vehicle Emissions/toxicity ; Vehicle Emissions/analysis ; Neurodegenerative Diseases
    Chemical Substances Particulate Matter ; Reactive Oxygen Species ; Vehicle Emissions
    Language English
    Publishing date 2024-02-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 2170936-1
    ISSN 1743-8977 ; 1743-8977
    ISSN (online) 1743-8977
    ISSN 1743-8977
    DOI 10.1186/s12989-024-00564-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Corrigendum to "Impairment of mitochondrial function by particulate matter: Implications for the brain" [Neurochem. Int. 135 (May 2020) 104694].

    Chew, Sweelin / Kolosowska, Natalia / Saveleva, Liudmila / Malm, Tarja / Kanninen, Katja M

    Neurochemistry international

    2020  Volume 139, Page(s) 104776

    Language English
    Publishing date 2020-07-28
    Publishing country England
    Document type Published Erratum
    ZDB-ID 283190-9
    ISSN 1872-9754 ; 0197-0186
    ISSN (online) 1872-9754
    ISSN 0197-0186
    DOI 10.1016/j.neuint.2020.104776
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Microglia Development and Maturation and Its Implications for Induction of Microglia-Like Cells from Human iPSCs

    Johannes Wurm / Henna Konttinen / Christian Andressen / Tarja Malm / Björn Spittau

    International Journal of Molecular Sciences, Vol 22, Iss 3088, p

    2021  Volume 3088

    Abstract: Microglia are resident immune cells of the central nervous system and play critical roles during the development, homeostasis, and pathologies of the brain. Originated from yolk sac erythromyeloid progenitors, microglia immigrate into the embryonic brain ...

    Abstract Microglia are resident immune cells of the central nervous system and play critical roles during the development, homeostasis, and pathologies of the brain. Originated from yolk sac erythromyeloid progenitors, microglia immigrate into the embryonic brain parenchyma to undergo final postnatal differentiation and maturation driven by distinct chemokines, cytokines, and growth factors. Among them, TGFβ1 is an important regulator of microglial functions, mediating homeostasis, anti-inflammation, and triggering the expression of microglial homeostatic signature genes. Since microglia studies are mainly based on rodent cells and the isolation of homeostatic microglia from human tissue is challenging, human-induced pluripotent stem cells have been successfully differentiated into microglia-like cells recently. However, employed differentiation protocols strongly vary regarding used cytokines and growth factors, culture conditions, time span, and cell yield. Moreover, the incomplete differentiation of human microglia can hamper the similarity to primary human microglia and dramatically influence the outcome of follow-up studies with these differentiated cells. This review summarizes the current knowledge of the molecular mechanisms driving rodent microglia differentiation in vivo, further compares published differentiation protocols, and highlights the potential of TGFβ as an essential maturation factor.
    Keywords microglia maturation ; TGFβ ; iPSC ; microglia-like cells ; hiMGLs ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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