Browsing by Subject "TRANSPORT"

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  • Baghirov, Habib; Karaman, Didem; Viitala, Tapani; Duchanoy, Alain; Lou, Yan-Ru; Mamaeva, Veronika; Pryazhnikov, Evgeny; Khiroug, Leonard; Davies, Catharina de Lange; Sahlgren, Cecilia; Rosenholm, Jessica M. (2016)
    Drug delivery into the brain is impeded by the blood-brain-barrier (BBB) that filters out the vast majority of drugs after systemic administration. In this work, we assessed the transport, uptake and cytotoxicity of promising drug nanocarriers, mesoporous silica nanoparticles (MSNs), in in vitro models of the BBB. RBE4 rat brain endothelial cells and Madin-Darby canine kidney epithelial cells, strain II, were used as BBB models. We studied spherical and rod-shaped MSNs with the following modifications: bare MSNs and MSNs coated with a poly (ethylene glycol)-poly(ethylene imine) (PEG-PEI) block copolymer. In transport studies, MSNs showed low permeability, whereas the results of the cellular uptake studies suggest robust uptake of PEG-PEI-coated MSNs. None of the MSNs showed significant toxic effects in the cell viability studies. While the shape effect was detectable but small, especially in the real-time surface plasmon resonance measurements, coating with PEG-PEI copolymers clearly facilitated the uptake of MSNs. Finally, we evaluated the in vivo detectability of one of the best candidates, i.e. the copolymer-coated rod-shaped MSNs, by two-photon in vivo imaging in the brain vasculature. The particles were clearly detectable after intravenous injection and caused no damage to the BBB. Thus, when properly designed, the uptake of MSNs could potentially be utilized for the delivery of drugs into the brain via transcellular transport.
  • Hentati-Sundberg, J.; Raymond, C.; Skoeld, M.; Svensson, O.; Gustafsson, B.; Bonaglia, S. (2020)
    Seabirds redistribute nutrients between different ecosystem compartments and over vast geographical areas. This nutrient transfer may impact both local ecosystems on seabird breeding islands and regional biogeochemical cycling, but these processes are seldom considered in local conservation plans or biogeochemical models. The island of Stora Karlso in the Baltic Sea hosts the largest concentration of piscivorous seabirds in the region, and also hosts a large colony of insectivorous House martins Delichon urbicum adjacent to the breeding seabirds. We show that a previously reported unusually high insectivore abundance was explained by large amounts of chironomids-highly enriched in delta N-15-that feed on seabird residues as larvae along rocky shores to eventually emerge as flying adults. Benthic ammonium and phosphate fluxes were up to 163% and 153% higher close to the colony (1,300 m distance) than further away (2,700 m) and the estimated nutrient release from the seabirds at were in the same order of magnitude as the loads from the largest waste-water treatment plants in the region. The trophic cascade impacting insectivorous passerines and the substantial redistribution of nutrients suggest that seabird nutrient transfer should be increasingly considered in local conservation plans and regional nutrient cycling models.
  • Laakso, Senja (2017)
    Despite recent political and scientific interest in experiments, there is little research on participants' experiences of experimentation. This article focuses on an experiment during which eleven participants gave up ownership of their cars, and in return, received free travel cards to local buses for six months. The experiment is analysed from two perspectives. Firstly, the impact of the experiment on carbon emissions of the participants' everyday mobility is estimated based on weekly mobility surveillances and travel card data. Secondly, the practice theoretical approach is used to study the change in participants' mobility routines. The results indicate that the processes of de- and re-routinisation depend on multiple structural and individual factors reinforcing each other. Although carbon emissions of everyday mobility were reduced because of the experiment, there was variation in how the new routines were (or were not) acquired among the participants. The article suggests that, when analysed from the practice perspective, experiments might work as tools for mutual learning on how to make local public transportation more attractive among residents. Attention should also be paid to reducing the need for driving in the first place, as well as to providing more support and services for car-free living. (C) 2017 Elsevier Ltd. All rights reserved.
  • Kim, Christine S.; Ding, Xiaolei; Allmeroth, Kira; Biggs, Leah C.; Kolenc, Olivia I.; L'Hoest, Nina; Chacon-Martinez, Carlos Andres; Edlich-Muth, Christian; Giavalisco, Patrick; Quinn, Kyle P.; Denzel, Martin S.; Eming, Sabine A.; Wickström, Sara A. (2020)
    Stem cells reside in specialized niches that are critical for their function. Upon activation, hair follicle stem cells (HFSCs) exit their niche to generate the outer root sheath (ORS), but a subset of ORS progeny returns to the niche to resume an SC state. Mechanisms of this fate reversibility are unclear. We show that the ability of ORS cells to return to the SC state requires suppression of a metabolic switch from glycolysis to oxidative phosphorylation and glutamine metabolism that occurs during early HFSC lineage progression. HFSC fate reversibility and glutamine metabolism are regulated by the mammalian target of rapamycin complex 2 (mTORC2)-Akt signaling axis within the niche. Deletion of mTORC2 results in a failure to re-establish the HFSC niche, defective hair follicle regeneration, and compromised long-term maintenance of HFSCs. These findings highlight the importance of spatiotemporal control of SC metabolic states in organ homeostasis.
  • Humborg, Christoph; Geibel, Marc. C.; Sun, Xiaole; McCrackin, Michelle; Mörth, Carl-Magnus; Stranne, Christian; Jakobsson, Martin; Gustafsson, Bo; Sokolov, Alexander; Norkko, Alf; Norkko, Joanna (2019)
    The summer heat wave in 2018 led to the highest recorded water temperatures since 1926 – up to 21 C – in bottom coastal waters of the Baltic Sea, with implications for the respiration patterns in these shallow coastal systems. We applied cavity ring-down spectrometer measurements to continuously monitor carbon dioxide (CO2) and methane (CH4) surface-water concentrations, covering the coastal archipelagos of Sweden and Finland and the open and deeper parts of the Northern Baltic Proper. This allowed us to i) follow an upwelling event near the Swedish coast leading to elevated CO2 and moderate CH4 outgassing, and ii) to estimate CH4 sources and fluxes along the coast by investigating water column inventories and air-sea fluxes during a storm and an associated downwelling event. At the end of the heat wave, before the storm event, we found elevated CO2 (1583 µatm) and CH4 (70 nmol/L) concentrations. During the storm, a massive CO2 sea-air flux of up to 274 mmol m-2 d-1 was observed. While water-column CO2 concentrations were depleted during several hours of the storm, CH4 concentrations remained elevated. Overall, we found a positive relationship between CO2 and CH4 wind-driven sea-air fluxes, however, the highest CH4 fluxes were observed at low winds whereas highest CO2 fluxes were during peak winds, suggesting different sources and processes controlling their fluxes besides wind. We applied a box-model approach to estimate the CH4 supply needed to sustain these elevated CH4 concentrations and the results suggest a large source flux of CH4 to the water column of 2.5 mmol m-2 d-1. These results are qualitatively supported by acoustic observations of vigorous and widespread outgassing from the sediments, with flares that could be traced throughout the water column penetrating the pycnocline and reaching the sea surface. The results suggest that the heat wave triggered CO2 and CH4 fluxes in the coastal zones that are comparable with maximum emission rates found in other hot spots, such as boreal and arctic lakes and wetlands. Further, the results suggest that heat waves are as important for CO2 and CH4 sea-air fluxes as the ice break up in spring.
  • Rödenbeck, C.; Zaehle, S.; Keeling, R.; Heimann, M. (2018)
    Interannual variations in the large-scale net ecosystem exchange (NEE) of CO2 between the terrestrial biosphere and the atmosphere were estimated for 1957-2017 from sustained measurements of atmospheric CO2 mixing ratios. As the observations are sparse in the early decades, available records were combined into a 'quasi-homogeneous' dataset based on similarity in their signals, to minimize spurious variations from beginning or ending data records. During El Nino events, CO2 is anomalously released from the tropical band, and a few months later also in the northern extratropical band. This behaviour can approximately be represented by a linear relationship of the NEE anomalies and local air temperature anomalies, with sensitivity coefficients depending on geographical location and season. The apparent climate sensitivity of global total NEE against variations in pan-tropically averaged annual air temperature slowly changed over time during the 1957-2017 period, first increasing (though less strongly than in previous studies) but then decreasing again. However, only part of this change can be attributed to actual changes in local physiological or ecosystem processes, the rest probably arising from shifts in the geographical area of dominating temperature variations. This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Nino on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.
  • Gungor, Burcin; Vanharanta, Lauri; Hölttä-Vuori, Maarit; Pirhonen, Juho; Petersen, Nikolaj H. T.; Gramolelli, Silvia; Ojala, Päivi M.; Kirkegaard, Thomas; Ikonen, Elina (2019)
    Objective: Heat Shock Proteins (HSPs) maintain cellular homeostasis under stress. HSP70 represents a major stress-inducible family member and has been identified as a druggable target in inherited cholesterol-sphingolipid storage diseases. We investigated if HSP70 modulates cholesterol accumulation in more common conditions related to atherogenesis. Methods: We studied the effects of recombinant HSP70 in cholesterol-laden primary macrophages from human blood donors and pharmacological HSP70 upregulation in high-cholesterol diet fed zebrafish. Results: Recombinant HSP70 facilitated cholesterol removal from primary human macrophage foam cells. RNA sequencing revealed that HSP70 induced a robust transcriptional re-programming, including upregulation of key targets of liver X receptors (LXR), master regulators of whole-body cholesterol removal. Mechanistically, HSP70 interacted with the macrophage LXRalpha promoter, increased LXRalpha and its target mRNAs, and led to elevated levels of key proteins facilitating cholesterol efflux, including ATP-binding cassette transporters A1 and G1. Pharmacological augmentation of endogenous HSP70 in high-cholesterol diet fed zebrafish activated LXR and its target mRNAs and reduced cholesterol storage at the whole organism level. Conclusion: These data demonstrate that HSP70 exerts a cholesterol lowering effect in primary human cells and animals and uncover a nuclear action of HSP70 in mediating cross-talk between HSP and LXR transcriptional regulation. (C) 2019 The Authors. Published by Elsevier GmbH.
  • Liu, Meijuan; Zhou, Chang; Lu, Feifei; Hu, Xiaohan (2021)
    With the development of ecological paradigm coupled with the relentless implementation of myriad environmental policies in China, the rapid development of carbon emission trading and carbon trading market has had a vital impact on the financial performance of enterprises at the microlevel. This study has sampled the A-share listed companies in China, from 2009 to 2018, and adopted the difference-in-difference (DID) method to investigate the effect of the carbon emission trading on corporate financial performance from the microlevel. Evidence showed that the implementation of carbon emission trading effectively improved the total asset-liability ratio of enterprises, though it reduced the value of the current capital market. Moreover, in the regions under strict legal environment, the enhancement effect of the total asset-liability ratio was more obvious, whereas in the regions under loose legal environment, the reduction effect of the value of the capital market was more obvious. Further analysis showed that the implementation of carbon emission trading could not promote Chinese enterprises to increase R&D investment. Hence the implementation of carbon emission trading has improved the level of non-business income of enterprises incorporated into the trading system, but its impact on the investment income of enterprises was not significant.
  • Helle, Inari; Mäkinen, Jussi Antti-Eerikki; Nevalainen, Maisa Katariina; Afenyo, Mawuli; Vanhatalo, Jarno (2020)
    Oil spills resulting from maritime accidents pose a poorly understood risk to the Arctic environment. We propose a novel probabilistic method to quantitatively assess these risks. Our method accounts for spatiotemporally varying population distributions, the spreading of oil, and seasonally varying species-specific exposure potential and sensitivity to oil. It quantifies risk with explicit uncertainty estimates, enables one to compare risks over large geographic areas, and produces information on a meaningful scale for decision-making. We demonstrate the method by assessing the short-term risks oil spills pose to polar bears, ringed seals, and walrus in the Kara Sea, the western part of the Northern Sea Route. The risks differ considerably between species, spatial locations, and seasons. Our results support current aspirations to ban heavy fuel oil in the Arctic but show that we should not underestimate the risks of lighter oils either, as these oils can pollute larger areas than heavier ones. Our results also highlight the importance of spatially explicit season-specific oil spill risk assessment in the Arctic and that environmental variability and the lack of data are a major source of uncertainty related to the oil spill impacts.
  • Luebtow, Michael M.; Oerter, Sabrina; Quader, Sabina; Jeanclos, Elisabeth; Cubukova, Alevtina; Krafft, Marion; Haider, Malik Salman; Schulte, Clemens; Meier, Laura; Rist, Maximilian; Sampetrean, Oltea; Kinoh, Hiroaki; Gohla, Antje; Kataoka, Kazunori; Appelt-Menzel, Antje; Luxenhofer, Robert (2020)
    Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase of the family of statins have been suggested as therapeutic options in various tumors. Atorvastatin is a statin with the potential to cross the blood-brain barrier; however, the concentrations necessary for a cytotoxic effect against cancer cells exceed the concentrations achievable via oral administration, which made the development of a novel atorvastatin formulation necessary. We characterized the drug loading and basic physicochemical characteristics of micellar atorvastatin formulations and tested their cytotoxicity against a panel of different glioblastoma cell lines. In addition, activity against tumor spheroids formed from mouse glioma and mouse cancer stem cells, respectively, was evaluated. Our results show good activity of atorvastatin against all tested cell lines. Interestingly, in the three-dimensional (3D) models, growth inhibition was more pronounced for the micellar formulation compared to free atorvastatin. Finally, atorvastatin penetration across a blood-brain barrier model obtained from human induced-pluripotent stem cells was evaluated. Our results suggest that the presented micelles may enable much higher serum concentrations than possible by oral administration; however, if transport across the blood-brain barrier is sufficient to reach the therapeutic atorvastatin concentration for the treatment of glioblastoma via intravenous administration remains unclear.
  • Watson, Victoria E.; Jacob, Megan E.; Bruno-Bárcena, José M.; Amirsultan, Sophia; Stauffer, Stephen H.; Píqueras, Victoria O.; Frias, Rafael; Gookin, Jody L. (2019)
    Typical enteropathogenic E. coli (tEPEC) carries the highest hazard of death in children with diarrhea and atypical EPEC (aEPEC) was recently identified as significantly associated with diarrheal mortality in kittens. In both children and kittens there is a significant association between aEPEC burden and diarrheal disease, however the infection can be found in individuals with and without diarrhea. It remains unclear to what extent, under what conditions, or by what mechanisms aEPEC serves as a primary pathogen in individuals with diarrhea. It seems likely that a combination of host and bacterial factors enable aEPEC to cause disease in some individuals and not in others. The purpose of this study was to determine the impact of aEPEC on intestinal function and diarrhea in kittens following experimentally-induced carriage and the influence of a disrupted intestinal microbiota on disease susceptibility. Results of this study identify aEPEC as a potential pathogen in kittens. In the absence of disruption to the intestinal microbiota, kittens are resistant to clinical signs of aEPEC carriage but demonstrate significant occult changes in intestinal absorption and permeability. Antibiotic-induced disruption of the intestinal microbiota prior to infection increases subsequent intestinal water loss as determined by % fecal wet weight. Enrichment of the intestinal microbiota with a commensal member of the feline mucosa-associated microbiota, Enterococcus hirae, ameliorated the effects of aEPEC experimental infection on intestinal function and water loss. These observations begin to unravel the mechanisms by which aEPEC infection may be able to exploit susceptible hosts.
  • Saarinen, Jukka; Sõzeri, Erkan; Fraser-Miller, Sara; Peltonen, Leena; A. Santos, Helder; Isomäki, Antti; Strachan, Clare J. (2017)
    We have used coherent anti-Stokes Raman scattering (CARS) microscopy as a novel and rapid, label-free and non-destructive imaging method to gain structural insights into live intestinal epithelial cell cultures used for drug permeability testing. Specifically we have imaged live Caco-2 cells in (bio)pharmaceutically relevant conditions grown on membrane inserts. Imaging conditions were optimized, including evaluation of suitable membrane materials and media solutions, as well as tolerable laser powers for non-destructive imaging of the live cells. Lipid structures, in particular lipid droplets, were imaged within the cells on the insert membranes. The size of the individual lipid droplets increased substantially over the 21-day culturing period up to approximately 10% of the volume of the cross section of individual cells. Variation in lipid content has important implications for intestinal drug permeation testing during drug development but has received limited attention to date due to a lack of suitable analytical techniques. CARS microscopy was shown to be well suited for such analysis with the potential for in situ imaging of the same individual cell-cultures that are used for permeation studies. Overall, the method may be used to provide important information about cell monolayer structure to better understand drug permeation results.
  • Niemisto, Juha; Lund-Hansen, Lars Chresten (2019)
    Climate change is leading to harsher resuspension events in shallow coastal environments influencing benthic nutrient fluxes. However, we lack information on the quantitative connection between these fluxes and the physical forces. Two identical experiments that were carried out both in May and August provided novel knowledge on the instantaneous effects of resuspension with known intensity on the benthic dissolved inorganic (phosphate: DIP, ammonium: NH4+, nitrite+nitrate: NOx, silicate, DSi) and organic nutrient (phosphorus: DOP, nitrogen: DON, carbon: DOC) fluxes in the shallow soft bottoms of the archipelago of Gulf of Finland (GoF), Baltic Sea. Resuspension treatments, as 2 times the critical shear stress, induced effluxes of one to two orders of magnitude higher than the diffusive fluxes from the studied oxic bottoms. The presence of oxygen resulted in newly formed iron oxyhydroxides and the subsequent precipitation/adsorption of the redox-dependent nutrients (DIP, DSi, organic nutrients) affecting their fluxes. Resuspension-induced NH4+ and NOx fluxes were associated with the organic content of sediments showing the highest values at the organic rich sites. NH4+ showed the strongest responses to resuspension treatments in August, but NOx at the time of high oxygen concentrations in near-bottom water in May. Foreseen increases in the frequency and intensity of resuspension events due to climate change will most likely enhance the internal nutrient loading of the studied coastal areas. The fluxes presented here, connected to known current velocities, can be utilized in modeling work and to assess and predict the internal nutrient loading following climate change.
  • JET Contributors; Eriksson, F.; Fransson, E.; Oberparleiter, M.; Nordman, H.; Strand, P.; Salmi, A.; Tala, T.; Ahlgren, T. (2019)
    Transport modelling of Joint European Torus (JET) dimensionless collisionality scaling experiments in various operational scenarios is presented. Interpretative simulations at a fixed radial position are combined with predictive JETTO simulations of temperatures and densities, using the TGLF transport model. The model includes electromagnetic effects and collisions as well as (E)over-right-arrow x (b)over-right-arrow shear in Miller geometry. Focus is on particle transport and the role of the neutral beam injection (NBI) particle source for the density peaking. The experimental 3-point collisionality scans include L-mode, and H-mode (D and H and higher beta D plasma) plasmas in a total of 12 discharges. Experimental results presented in (Tala et al 2017 44th EPS Conf.) indicate that for the H-mode scans, the NBI particle source plays an important role for the density peaking, whereas for the L-mode scan, the influence of the particle source is small. In general, both the interpretative and predictive transport simulations support the experimental conclusions on the role of the NBI particle source for the 12 JET discharges.
  • Guard, Blake C.; Honneffer, Julia B.; Jergens, Albert E.; Jonika, Michelle M.; Toresson, Linda; Lawrence, Yuri A.; Webb, Craig B.; Hill, Steve; Lidbury, Jonathan A.; Steiner, Joerg M.; Suchodolski, Jan S. (2019)
    Abstract Background Mounting evidence from human studies suggests that bile acid dysmetabolism might play a role in various human chronic gastrointestinal diseases. It is unknown whether fecal bile acid dysmetabolism occurs in dogs with chronic inflammatory enteropathy (CE). Objective To assess microbial dysbiosis, fecal unconjugated bile acids (fUBA), and disease activity in dogs with steroid-responsive CE. Animals Twenty-four healthy control dogs and 23 dogs with steroid-responsive CE. Methods In this retrospective study, fUBA were measured and analyzed. Fecal microbiota were assessed using a dysbiosis index. The canine inflammatory bowel disease activity index was used to evaluate remission of clinical signs. This was a multi-institutional study where dogs with steroid-responsive CE were evaluated over time. Results The dysbiosis index was increased in dogs with CE (median, 2.5; range, ?6.2 to 6.5) at baseline compared with healthy dogs (median, ?4.5; range, ?6.5 to ?2.6; P?=?.002) but did not change in dogs with CE over time. Secondary fUBA were decreased in dogs with CE (median, 29%; range, 1%-99%) compared with healthy dogs (median, 88%; 4%-96%; P?=?.049). The percent of secondary fUBA in dogs with CE increased from baseline values (median, 28%; range, 1%-99%) after 2-3?months of treatment (median, 94%; range, 1%-99%; P?=?0.0183). Conclusions and Clinical Importance These findings suggest that corticosteroids regulate fecal bile acids in dogs with CE. Additionally, resolution of clinical activity index in dogs with therapeutically managed CE and bile acid dysmetabolism are likely correlated. However, subclinical disease (i.e., microbial dysbiosis) can persist in dogs with steroid-responsive CE.
  • Heybrock, Saskia; Kanerva, Kristiina; Meng, Ying; Ing, Chris; Liang, Anna; Xiong, Zi-Jian; Weng, Xialian; Kim, Young Ah; Collins, Richard; Trimble, William; Pomes, Regis; Prive, Gilbert G.; Annaert, Wim; Schwake, Michael; Heeren, Joerg; Lullmann-Rauch, Renate; Grinstein, Sergio; Ikonen, Elina; Saftig, Paul; Neculai, Dante (2019)
    The intracellular transport of cholesterol is subject to tight regulation. The structure of the lysosomal integral membrane protein type 2 (LIMP-2, also known as SCARB2) reveals a large cavity that traverses the molecule and resembles the cavity in SR-B1 that mediates lipid transfer. The detection of cholesterol within the LIMP-2 structure and the formation of cholesterol - like inclusions in LIMP-2 knockout mice suggested the possibility that LIMP2 transports cholesterol in lysosomes. We present results of molecular modeling, crosslinking studies, microscale thermophoresis and cell-based assays that support a role of LIMP-2 in cholesterol transport. We show that the cavity in the luminal domain of LIMP-2 can bind and deliver exogenous cholesterol to the lysosomal membrane and later to lipid droplets. Depletion of LIMP-2 alters SREBP-2-mediated cholesterol regulation, as well as LDL-receptor levels. Our data indicate that LIMP-2 operates in parallel with Niemann Pick (NPC)-proteins, mediating a slower mode of lysosomal cholesterol export.
  • Lettenmeier, Michael; Hirvilammi, Tuuli; Laakso, Senja; Lahteenoja, Satu; Aalto, Kristiina (2012)
    The article assesses the material footprints of households living on a minimum amount of social benefits in Finland and discusses the consequences in terms of ecological and social sustainability. The data were collected using interviews and a questionnaire on the consumption patterns of 18 single households. The results are compared to a study on households with varying income levels, to average consumption patterns and to decent minimum reference budgets. The low-income households have lower material footprints than average and most of the material footprints are below the socially sustainable level of consumption, which is based on decent minimum reference budgets. However, the amount of resources used by most of the households studied here is still at least double that required for ecological sustainability. The simultaneous existence of both deprivation and overconsumption requires measures from both politicians and companies to make consumption sustainable. For example, both adequate housing and economic mobility need to be addressed. Measures to improve the social sustainability of low-income households should target reducing the material footprints of more affluent households. Furthermore, the concept of what constitutes a decent life should be understood more universally than on the basis of standards of material consumption.
  • Snellman, J. E.; Rheinhardt, M.; Käpylä, P. J.; Mantere, M. J.; Brandenburg, A. (2012)
  • Ikonen, Elina (2018)
    This review discusses advances in understanding how the controlled delivery of cholesterol between subcellular compartments is achieved and what novel experimental strategies are being employed to address this fundamental question. Recent work has focused on cholesterol-binding proteins that can facilitate directional cholesterol transfer between contacts of the ER and Golgi or late endosomal membranes. Increasing structural information on cholesterol-binding proteins, new modules engineered from them as well as improved imaging and gene editing techniques are providing valuable insights. There is also mounting information on how the crosstalk between cholesterol transport and nutrient signaling is orchestrated and how cellular fatty acid metabolism and cholesterol homeostasis are intertwined.