Browsing by Subject "INFECTIOUS-DISEASES"

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  • Koivu-Jolma, Mikko; Annila, Arto (2018)
    Mathematical epidemiology is a well-recognized discipline to model infectious diseases. It also provides guidance for public health officials to limit outbreaks. Nevertheless, epidemics take societies by surprise every now and then, for example, when the Ebola virus epidemic raged seemingly unrestrained in Western Africa. We provide insight to this capricious character of nature by describing the epidemic as a natural process, i.e., a phenomenon governed by thermodynamics. Our account, based on statistical mechanics of open systems, clarifies that it is impossible to predict accurately epidemic courses because everything depends on everything else. Nonetheless, the thermodynamic theory yields a comprehensive and analytical view of the epidemic. The tenet subsumes various processes in a scale-free manner from the molecular to the societal levels. The holistic view accentuates overarching procedures in arresting and eradicating epidemics.
  • Saari, H.; Lisitsyna, Ekaterina S.; Rautaniemi, K.; Rojalin, T.; Niemi, L.; Nivaro, O.; Laaksonen, T.; Yliperttula, M.; Vuorimaa-Laukkanen, E. (2018)
    In response to physiological and artificial stimuli, cells generate nano-scale extracellular vesicles (EVs) by encapsulating biomolecules in plasma membrane-derived phospholipid envelopes. These vesicles are released to bodily fluids, hence acting as powerful endogenous mediators in intercellular signaling. EVs provide a compelling alternative for biomarker discovery and targeted drug delivery, but their kinetics and dynamics while interacting with living cells are poorly understood. Here we introduce a novel method, fluorescence lifetime imaging microscopy (FLIM) to investigate these interaction attributes. By FLIM, we show distinct cellular uptake mechanisms of different EV subtypes, exosomes and microvesicles, loaded with anti-cancer agent, paclitaxel. We demonstrate differences in intracellular behavior and drug release profiles of paclitaxel-containing EVs. Exosomes seem to deliver the drug mostly by endocytosis while microvesicles enter the cells by both endocytosis and fusion with cell membrane. This research offers a new real-time method to investigate EV kinetics with living cells, and it is a potential advancement to complement the existing techniques. The findings of this study improve the current knowledge in exploiting EVs as next-generation targeted drug delivery systems.
  • Hannula-Jouppi, Katariina; Massinen, Satu; Siljander, Tuula; Mäkelä, Siru Päivikki; Kivinen, Katja; Leinonen, Rasko; Jiao, Hong; Aitos, Paivi; Karppelin, Matti; Vuopio, Jaana; Syrjanen, Jaana; Kere, Juha (2013)
  • van Belkum, Alex; Almeida, Carina; Bardiaux, Benjamin; Barrass, Sarah V.; Butcher, Sarah J.; Caykara, Tugce; Chowdhury, Sounak; Datar, Rucha; Eastwood, Ian; Goldman, Adrian; Goyal, Manisha; Happonen, Lotta; Izadi-Pruneyre, Nadia; Jacobsen, Theis; Johnson, Pirjo H.; Kempf, Volkhard A. J.; Kiessling, Andreas; Bueno, Juan Leva; Malik, Anchal; Malmstrom, Johan; Meuskens, Ina; Milner, Paul A.; Nilges, Michael; Pamme, Nicole; Peyman, Sally A.; Rodrigues, Ligia R.; Rodriguez-Mateos, Pablo; Sande, Maria G.; Silva, Carla Joana; Stasiak, Aleksandra Cecylia; Stehle, Thilo; Thibau, Arno; Vaca, Diana J.; Linke, Dirk (2021)
    Infectious diseases are an existential health threat, potentiated by emerging and re-emerging viruses and increasing bacterial antibiotic resistance. Targeted treatment of infectious diseases requires precision diagnostics, especially in cases where broad-range therapeutics such as antibiotics fail. There is thus an increasing need for new approaches to develop sensitive and specific in vitro diagnostic (IVD) tests. Basic science and translational research are needed to identify key microbial molecules as diagnostic targets, to identify relevant host counterparts, and to use this knowledge in developing or improving IVD. In this regard, an overlooked feature is the capacity of pathogens to adhere specifically to host cells and tissues. The molecular entities relevant for pathogen-surface interaction are the so-called adhesins. Adhesins vary from protein compounds to (poly-)saccharides or lipid structures that interact with eukaryotic host cell matrix molecules and receptors. Such interactions co-define the specificity and sensitivity of a diagnostic test. Currently, adhesin-receptor binding is typically used in the pre-analytical phase of IVD tests, focusing on pathogen enrichment. Further exploration of adhesin-ligand interaction, supported by present high-throughput "omics" technologies, might stimulate a new generation of broadly applicable pathogen detection and characterization tools. This review describes recent results of novel structure-defining technologies allowing for detailed molecular analysis of adhesins, their receptors and complexes. Since the host ligands evolve slowly, the corresponding adhesin interaction is under selective pressure to maintain a constant receptor binding domain. IVD should exploit such conserved binding sites and, in particular, use the human ligand to enrich the pathogen. We provide an inventory of methods based on adhesion factors and pathogen attachment mechanisms, which can also be of relevance to currently emerging pathogens, including SARS-CoV-2, the causative agent of COVID-19.
  • Pirilä, Satu Maaria; Taskinen, Mervi; Viljakainen, Heli; Kajosaari, Merja; Turanlahti, Maila; Saarinen-Pihkala, Ulla M.; Mäkitie, Outi (2011)
  • Heikkilä, Anna-Riitta; Elovainio, Marko; Raaska, Hanna; Matomäki, Jaakko; Sinkkonen, Jari; Lapinleimu, Helena (2021)
    Aim At arrival in new home country, internationally adopted children often have intestinal parasites. International adoptees also exhibit more behavioral problems than their biological peers. We examined whether intestinal parasite infections in international adoptees on arrival in Finland are associated with their later behavioral and emotional problems. Methods Data for this study were sourced from the Finnish Adoption Study (FinAdo) based on parental questionnaires for all internationally adopted children under 18 years (n = 1450) who arrived in Finland from 1985 to 2007. A total of 1293 families provided sufficient information on the adoptee's background, parasitic status on arrival, and behavioral symptoms at the median time of 5 years after arrival (mean age = 7.8 years). Behavioral and emotional disorders were evaluated with the Child Behavior Checklist (CBCL). Statistical analyses were conducted using linear regression. Results Of the 1293 families, parents of 206 adoptive children reported intestinal parasites in their adopted children on arrival. Parasite-infected children had subsequently higher CBCL problem scores than the children without parasites (p <0.001). The association between intestinal parasites and later behavioral problems was stronger than that between intestinal parasites and any other factors measured in this study, except disability. Limitations The control group was naturally provided by the adopted children without parasite infections, but we could not compare the adopted children to non-adopted children without a defined parasite infection. We were unable to specify the effects associated with a specific parasite type. It was not possible either to include multiple environmental factors that could have been associated with behavioral problems in the models, which indicated only modest explanatory values. Conclusions In this study, intestinal parasite infections in early childhood may be associated with children's later psychological wellbeing, even in children who move to a country with a low prevalence of parasites. Our findings may support further developments pertaining to the gut-brain theory.
  • Lilley, Thomas M.; Prokkola, Jenni M.; Blomberg, Anna S.; Paterson, Steve; Johnson, Joseph S.; Turner, Gregory G.; Bartonička, Tomáš; Bachorec, Erik; Reeder, DeeAnn M.; Field, Kenneth A. (2019)
    Resistance and tolerance allow organisms to cope with potentially life-threatening pathogens. Recently introduced pathogens initially induce resistance responses, but natural selection favors the development of tolerance, allowing for a commensal relationship to evolve. Mycosis by Pseudogymnoascus destructans, causing white-nose syndrome (WNS) in Nearctic hibernating bats, has resulted in population declines since 2006. The pathogen, which spread from Europe, has infected species of Palearctic Myotis for a longer period. We compared ecologically relevant responses to the fungal infection in the susceptible Nearctic M. lucifugus and less susceptible Palearctic M. myotis, to uncover factors contributing to survival differences in the two species. Samples were collected from euthermic bats during arousal from hibernation, a naturally occurring phenomenon, during which transcriptional responses are activated. We compared the whole-transcriptome responses in wild bats infected with P. destructans hibernating in their natural habitat. Our results show dramatically different local transcriptional responses to the pathogen between uninfected and infected samples from the two species. Whereas we found 1526 significantly upregulated or downregulated transcripts in infected M. lucifugus, only one transcript was downregulated in M. myotis. The upregulated response pathways in M. lucifugus include immune cell activation and migration, and inflammatory pathways, indicative of an unsuccessful attempt to resist the infection. In contrast, M. myotis appears to tolerate P. destructans infection by not activating a transcriptional response. These host-microbe interactions determine pathology, contributing to WNS susceptibility, or commensalism, promoting tolerance to fungal colonization during hibernation that favors survival.
  • Savolainen-Kopra, Carita; Haapakoski, Jaason; Peltola, Piia A.; Ziegler, Thedi; Korpela, Terttu; Anttila, Pirjo; Amiryousefi, Ali; Huovinen, Pentti; Huvinen, Markku; Noronen, Heikki; Riikkala, Pia; Roivainen, Merja; Ruutu, Petri; Teirila, Juha; Vartiainen, Erkki; Hovi, Tapani (2010)
  • Penczykowski, Rachel M.; Laine, Anna-Liisa; Koskella, Britt (2016)
    Predicting the emergence, spread and evolution of parasites within and among host populations requires insight to both the spatial and temporal scales of adaptation, including an understanding of within-host up through community-level dynamics. Although there are very few pathosystems for which such extensive data exist, there has been a recent push to integrate studies performed over multiple scales or to simultaneously test for dynamics occurring across scales. Drawing on examples from the literature, with primary emphasis on three diverse host-parasite case studies, we first examine current understanding of the spatial structure of host and parasite populations, including patterns of local adaptation and spatial variation in host resistance and parasite infectivity. We then explore the ways to measure temporal variation and dynamics in host-parasite interactions and discuss the need to examine change over both ecological and evolutionary timescales. Finally, we highlight new approaches and syntheses that allow for simultaneous analysis of dynamics across scales. We argue that there is great value in examining interplay among scales in studies of host-parasite interactions.