| 1. |
- Campbell, Kate, 1987, et al.
(author)
-
Cell-to-cell heterogeneity emerges as consequence of metabolic cooperation in a synthetic yeast community
- 2016
-
In: Biotechnology journal. - : Wiley. - 1860-6768 .- 1860-7314. ; 11:9, s. 1169-1178
-
Journal article (peer-reviewed)abstract
- Cells that grow together respond heterogeneously to stress even when they are genetically similar. Metabolism, a key determinant of cellular stress tolerance, may be one source of this phenotypic heterogeneity, however, this relationship is largely unclear. We used self-establishing metabolically cooperating (SeMeCo) yeast communities, in which metabolic cooperation can be followed on the basis of genotype, as a model to dissect the role of metabolic cooperation in single-cell heterogeneity. Cells within SeMeCo communities showed to be highly heterogeneous in their stress tolerance, while the survival of each cell under heat or oxidative stress, was strongly determined by its metabolic specialization. This heterogeneity emerged for all metabolite exchange interactions studied (histidine, leucine, uracil, and methionine) as well as oxidant (H2O2, diamide) and heat stress treatments. In contrast, the SeMeCo community collectively showed to be similarly tolerant to stress as wild-type populations. Moreover, stress heterogeneity did not establish as sole consequence of metabolic genotype (auxotrophic background) of the single cell, but was observed only for cells that cooperated according to their metabolic capacity. We therefore conclude that phenotypic heterogeneity and cell to cell differences in stress tolerance are emergent properties when cells cooperate in metabolism.
|
|
| 2. |
- Frenning, Göran, et al.
(author)
-
Dielectric and Li transport properties of electron conducting and non-conducting sputtered amorphous Ta2O5 films
- 2001
-
In: Electrochimica Acta. - 0013-4686 .- 1873-3859. ; 46:13-14, s. 2041-2046
-
Journal article (peer-reviewed)abstract
- Two types of sputtered thin film amorphous tantalum oxide (Ta2O5) were studied: one electron conducting Ta2O5 (ec-Ta2O5) and the other non-conducting Ta2O5 (nc-Ta2O5). The as-deposited films were characterized by impedance spectroscopy (IS) and isothermal transient ionic current (ITIC) measurements. From IS, the dc conductivity 2×10−14 S/cm was obtained for the ec-Ta2O5 film at an applied ac potential of 50 mV whereas a value ≤1×10−17 S/cm was obtained for the nc-Ta2O5 film. Li conducting properties were studied using the galvanostatic intermittent titration technique and ITIC measurements on the intercalated samples. Despite the very dissimilar dc conductivities of the as-deposited films, the two Ta2O5 samples showed surprisingly similar Li ion conducting properties for small Li/Ta2O5 ratios. The Li ion mobility was in the range 1.1×10−9–3.0×10−9 cm2/V s for both films. However, the Li storage behaviour as well as the chemical diffusion coefficient differed. For the nc-Ta2O5 film a plateau was observed in the equilibrium potential vs. composition curve for Li/Ta2O5 ratios between 7×10−5 and 2×10−3. This plateau was likely to have been caused by attractive interactions between the intercalated ions, possibly large enough to cause phase separation. The attractive interactions were shown to suppress the chemical diffusion coefficient in this composition range.
|
|
| 3. |
- Latvala, S., et al.
(author)
-
Dynamin inhibition interferes with inflammasome activation and cytokine gene expression in Streptococcus pyogenes-infected human macrophages
- 2014
-
In: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 178:2, s. 320-333
-
Journal article (peer-reviewed)abstract
- In the present study, we have analysed the ability of Streptococcus pyogenes [Group A streptococcus (GAS)] to activate the NACHT-domain-, leucinerich repeat-and PYD-containing protein 3 (NALP3) inflammasome complex in human monocyte-derived macrophages and the molecules and signalling pathways involved in GAS-induced inflammatory responses. We focused upon analysing the impact of dynamin-dependent endocytosis and the role of major streptococcal virulence factors streptolysin O (SLO) and streptolysin S (SLS) in the immune responses induced by GAS. These virulence factors are involved in immune evasion by forming pores in host cell membranes, and aid the bacteria to escape from the endosome-lysosome pathway. We analysed cytokine gene expression in human primary macrophages after stimulation with live or inactivated wild-type GAS as well as with live SLO and SLS defective bacteria. Interleukin (IL)-1 beta, IL-10, tumour necrosis factor (TNF)-alpha and chemokine (C-X-C motif) ligand (CXCL)-10 cytokines were produced after bacterial stimulation in a dose-dependent manner and no differences in cytokine levels were seen between live, inactivated or mutant bacteria. These data suggest that streptolysins or other secreted bacterial products are not required for the inflammatory responses induced by GAS. Our data indicate that inhibition of dynamin-dependent endocytosis in macrophages attenuates the induction of IL-1 beta, TNF-alpha, interferon (IFN)-beta and CXCL-10 mRNAs. We also observed that pro-IL-1 beta protein was expressed and efficiently cleaved into mature-IL-1 beta via inflammasome activation after bacterial stimulation. Furthermore, we demonstrate that multiple signalling pathways are involved in GAS-stimulated inflammatory responses in human macrophages.
|
|
| 4. |
- Lee, Christine J., et al.
(author)
-
Clinical manifestations of COVID-19 breakthrough infections: A systematic review and meta-analysis
- 2022
-
In: Journal of Medical Virology. - : WILEY. - 0146-6615 .- 1096-9071. ; 94:9, s. 4234-4245
-
Research review (peer-reviewed)abstract
- To provide a comparative meta-analysis and systematic review of the risk and clinical outcomes of coronavirus 2019 (COVID-19) infection between fully vaccinated and unvaccinated groups. Eighteen studies of COVID-19 infections in fully vaccinated ("breakthrough infections") and unvaccinated individuals were reviewed from Medline/PubMed, Scopus, Embase, and Web of Science databases. The meta-analysis examined the summary effects and between-study heterogeneity regarding differences in the risk of infection, hospitalization, treatments, and mortality between vaccinated and unvaccinated individuals. he overall risk of infection was lower for the fully vaccinated compared to that of the unvaccinated (relative risk [RR] 0.20, 95% confidence interval [CI]: 0.19-0.21), especially for variants other than Delta (Delta: RR 0.29, 95% CI: 0.13-0.65; other variants: RR 0.06, 95% CI: 0.04-0.08). The risk of asymptomatic infection was not statistically significantly different between fully vaccinated and unvaccinated (RR 0.56, 95% CI: 0.27-1.19). There were neither statistically significant differences in risk of hospitalization (RR 1.06, 95% CI: 0.38-2.93), invasive mechanical ventilation (RR 1.65, 95% CI: 0.90-3.06), or mortality (RR 1.19, 95% CI: 0.79-1.78). Conversely, the risk of supplemental oxygen during hospitalization was significantly higher for the unvaccinated (RR 1.40, 95% CI: 1.08-1.82). Unvaccinated people were more vulnerable to COVID-19 infection than fully vaccinated for all variants. Once infected, there were no statistically significant differences in the risk of hospitalization, invasive mechanical ventilation, or mortality. Still, unvaccinated showed an increased need for oxygen supplementation. Further prospective analysis, including patients risk factors, COVID-19 variants, and the utilized treatment strategies, would be warranted.
|
|
| 5. |
|
|
| 6. |
- Loyen, Anne, et al.
(author)
-
Sedentary Time and Physical Activity Surveillance Through Accelerometer Pooling in Four European Countries
- 2017
-
In: Sports Medicine. - : Springer Science and Business Media LLC. - 0112-1642 .- 1179-2035. ; 47:7, s. 1421-1435
-
Journal article (peer-reviewed)abstract
- Objective: The objective of this study was to pool, harmonise and re-analyse national accelerometer data from adults in four European countries in order to describe population levels of sedentary time and physical inactivity. Methods: Five cross-sectional studies were included from England, Portugal, Norway and Sweden. ActiGraph accelerometer count data were centrally processed using the same algorithms. Multivariable logistic regression analyses were conducted to study the associations of sedentary time and physical inactivity with sex, age, weight status and educational level, in both the pooled sample and the separate study samples. Results: Data from 9509 participants were used. On average, participants were sedentary for 530 min/day, and accumulated 36 min/day of moderate to vigorous intensity physical activity. Twenty-three percent accumulated more than 10 h of sedentary time/day, and 72% did not meet the physical activity recommendations. Nine percent of all participants were classified as high sedentary and low active. Participants from Norway showed the highest levels of sedentary time, while participants from England were the least physically active. Age and weight status were positively associated with sedentary time and not meeting the physical activity recommendations. Men and higher-educated people were more likely to be highly sedentary, while women and lower-educated people were more likely to be inactive. Conclusions: We found high levels of sedentary time and physical inactivity in four European countries. Older people and obese people were most likely to display these behaviours and thus deserve special attention in interventions and policy planning. In order to monitor these behaviours, accelerometer-based cross-European surveillance is recommended.
|
|
| 7. |
- Yao, Honghong, et al.
(author)
-
Molecular mechanisms involving sigma receptor-mediated induction of MCP-1: implication for increased monocyte transmigration.
- 2010
-
In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 115:23, s. 4951-62
-
Journal article (peer-reviewed)abstract
- Cocaine abuse hastens the neurodegeneration often associated with advanced HIV-1 infection. The mechanisms, in part, revolve around the neuroinflammatory processes mediated by the chemokine monocyte chemotactic protein-1 (MCP-1/CCL2). Understanding factors that modulate MCP-1 and, in turn, facilitate monocyte extravasation in the brain is thus of paramount importance. We now demonstrate that cocaine induces MCP-1 in rodent microglia through translocation of the sigma receptor to the lipid raft microdomains of the plasma membrane. Sequential activation of Src, mitogen-activated protein kinases (MAPKs), and phosphatidylinositol-3' kinase (PI3K)/Akt and nuclear factor kappaB (NF-kappaB) pathways resulted in increased MCP-1 expression. Furthermore, conditioned media from cocaine-exposed microglia increased monocyte transmigration, and thus was blocked by antagonists for CCR2 or sigma receptor. These findings were corroborated by demonstrating increased monocyte transmigration in mice exposed to cocaine, which was attenuated by pretreatment of mice with the sigma receptor antagonist. Interestingly, cocaine-mediated transmigratory effects were not observed in CCR2 knockout mice. We conclude that cocaine-mediated induction of MCP-1 accelerates monocyte extravasation across the endothelium. Understanding the regulation of MCP-1 expression and functional changes by cocaine/sigma receptor system may provide insights into the development of potential therapeutic targets for HIV-1-associated neurocognitive disorders.
|
|
| 8. |
- Özkaya Sahin, Gülsen, et al.
(author)
-
Effect of Complement on HIV-2 Plasma Antiviral Activity Is Intratype Specific and Potent
- 2013
-
In: Journal of Virology. - 1098-5514. ; 87:1, s. 273-281
-
Journal article (peer-reviewed)abstract
- Human immunodeficiency virus type-2 (HIV-2) infected individuals develop immunodeficiency with a considerable delay and transmit the virus at a lower rate as compared to HIV-1 infected. Conceivably, comparative studies on immune responsiveness of the HIV-1 and HIV-2 infected hosts may help to explain differences in pathogenesis and transmission between the two types of infection. Previous studies have shown that the neutralizing antibody response is more potent and broader in HIV-2 than HIV-1 infection. In the present study we have further examined the function of the humoral immune response and studied the potentiating effect of complement (C') on antiviral activity of plasma from singly HIV-1 or HIV-2 infected, as well as HIV-1/HIV-2 dually infected individuals. Neutralization and antibody-dependent complement-mediated inactivation of HIV-1 and HIV-2 isolates were tested in a plaque reduction assay using U87.CD4-CCR5 cells. Results showed that addition of C' increased intra-type antiviral activity of both HIV-1 and HIV-2 plasma, although the C' effect was more pronounced with HIV-2 than HIV-1 plasma. Using the area-under-curve (AUC)-based readout, multivariate statistical analysis confirmed that type of HIV infection was independently associated with the magnitude of the C' effect. Analysis carried out with purified IgG indicated that the C' effect was largely exerted through the classical C' pathway involving IgG in both HIV-1 and HIV-2 infections. In summary, these findings suggest that antibody binding to HIV-2 structures facilitates efficient use of C', and may thereby be one factor contributing to a strong antiviral activity present in HIV-2 infection.
|
|
| 9. |
|
|
| 10. |
|
|
