| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- van de Sande-Bruinsma, Nienke, et al.
(författare)
-
Antimicrobial drug use and resistance in Europe
- 2008
-
Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 14:11, s. 1722-30
-
Tidskriftsartikel (refereegranskat)abstract
- Our study confronts the use of antimicrobial agents in ambulatory care with the resistance trends of 2 major pathogens, Streptococcus pneumoniae and Escherichia coli, in 21 European countries in 2000-2005 and explores whether the notion that antimicrobial drug use determines resistance can be supported by surveillance data at national aggregation levels. The data obtained from the European Surveillance of Antimicrobial Consumption and the European Antimicrobial Resistance Surveillance System suggest that variation of consumption coincides with the occurrence of resistance at the country level. Linear regression analysis showed that the association between antimicrobial drug use and resistance was specific and robust for 2 of 3 compound pathogen combinations, stable over time, but not sensitive enough to explain all of the observed variations. Ecologic studies based on routine surveillance data indicate a relation between use and resistance and support interventions designed to reduce antimicrobial drug consumption at a national level in Europe.
|
|
| 5. |
|
|
| 6. |
- Davey, Norman E., et al.
(författare)
-
Discovery of short linear motif-mediated interactions through phage display of intrinsically disordered regions of the human proteome
- 2017
-
Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 284:3, s. 485-498
-
Tidskriftsartikel (refereegranskat)abstract
- The intrinsically disordered regions of eukaryotic proteomes are enriched in short linear motifs (SLiMs), which are of crucial relevance for cellular signaling and protein regulation; many mediate interactions by providing binding sites for peptide-binding domains. The vast majority of SLiMs remain to be discovered highlighting the need for experimental methods for their large-scale identification. We present a novel proteomic peptide phage display (ProP-PD) library that displays peptides representing the disordered regions of the human proteome, allowing direct large-scale interrogation of most potential binding SLiMs in the proteome. The performance of the ProP-PD library was validated through selections against SLiM-binding bait domains with distinct folds and binding preferences. The vast majority of identified binding peptides contained sequences that matched the known SLiM-binding specificities of the bait proteins. For SHANK1 PDZ, we establish a novel consensus TxF motif for its non-C-terminal ligands. The binding peptides mostly represented novel target proteins, however, several previously validated protein-protein interactions (PPIs) were also discovered. We determined the affinities between the VHS domain of GGA1 and three identified ligands to 40-130 mu M through isothermal titration calorimetry, and confirmed interactions through coimmunoprecipitation using full-length proteins. Taken together, we outline a general pipeline for the design and construction of ProP-PD libraries and the analysis of ProP-PD-derived, SLiM-based PPIs. We demonstrated the methods potential to identify low affinity motif-mediated interactions for modular domains with distinct binding preferences. The approach is a highly useful complement to the current toolbox of methods for PPI discovery.
|
|
| 7. |
|
|
| 8. |
- Markova, E, et al.
(författare)
-
Microwaves from GSM mobile telephones affect 53BP1 and gamma-H2AX foci in human lymphocytes from hypersensitive and healthy persons
- 2005
-
Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 113:9, s. 1172-1177
-
Tidskriftsartikel (refereegranskat)abstract
- The data on biologic effects of nonthermal microwaves (MWs) from mobile telephones are diverse, and these effects are presently ignored by safety standards of the International Commission for Non-Ionizing Radiation Protection (ICNIRP). In the present study, we investigated effects of MWs of Global System for Mobile Communication (GSM) at different carrier frequencies on human lymphocytes from healthy persons and from persons reporting hypersensitivity to electromagnetic fields (EMFs). We measured the changes in chromatin conformation, which are indicative of stress response and genotoxic effects, by the method of anomalous viscosity time dependence, and we analyzed tumor suppressor p53-binding protein 1 (53BP1) and phosphorylated histone H2AX (gamma-H2AX), which have been shown to colocalize in distinct foci with DNA double-strand breaks (DSBs), using immunofluorescence confocal laser microscopy. We found that MWs from GSM mobile telephones affect chromatin conformation and 53BP1/gamma-H2AX foci similar to heat shock. For the first time, we report here that effects of MWs from mobile telephones on human lymphocytes are dependent on carrier frequency. On average, the same response was observed in lymphocytes from hypersensitive and healthy subjects.
|
|
| 9. |
- Matsson, Pär, et al.
(författare)
-
Discovery of regulatory elements in human ATP-binding cassette transporters through expression quantitative trait mapping
- 2012
-
Ingår i: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 12, s. 214-226
-
Tidskriftsartikel (refereegranskat)abstract
- ATP-binding cassette (ABC) membrane transporters determine the disposition of many drugs, metabolites and endogenous compounds. Coding region variation in ABC transporters is the cause of many genetic disorders, but much less is known about the genetic basis and functional outcome of ABC transporter expression level variation. We used genotype and mRNA transcript level data from human lymphoblastoid cell lines to assess population and gender differences in ABC transporter expression, and to guide the discovery of genomic regions involved in transcriptional regulation. Nineteen of 49 ABC genes were differentially expressed between individuals of African, Asian and European descent, suggesting an important influence of race on expression level of ABC transporters. Twenty-four significant associations were found between transporter transcript levels and proximally located genetic variants. Several of the associations were experimentally validated in reporter assays. Through influencing ABC expression levels, these single-nucleotide polymorphisms may affect disease susceptibility and response to drugs.
|
|
| 10. |
- Najdenski, H, et al.
(författare)
-
Attenuation and preserved immunogenic potential of Yersinia pseudotuberculosis mutant strains evidenced in oral pig model
- 2009
-
Ingår i: Zoonoses and Public Health. - : John Wiley & Sons. - 1863-1959 .- 1863-2378. ; 56:4, s. 157-168
-
Tidskriftsartikel (refereegranskat)abstract
- Experimental oral infection of pigs with a parental Yersinia pseudotuberculosis strain pIB102, serotype O:3 and two mutant isogenic strains - pIB155,DeltayopK and pIB44,DeltaypkA has been carried out. Clinical findings, microbiological and immunological parameters were examined in dynamics from day 7 to day 60 post-infection (p.i.). All types of infections ran asymptomatically, without hyperthermia, loss of appetite, etc. Experiments on the blood parameters demonstrated a transient leucocytosis with lymphocytosis and monocytosis better expressed after yopK infection. Even though pig is usually known as a reservoir of yersiniae, bacterial colonization was found in mesenterial lymph nodes and tonsils on day 7, respectively 14 p.i. with parental strain, and only in tonsils on day 14 p.i. with both mutant strains. The augmented sensitivity of mutants to the bactericidal effect of leukocytes and blood sera is the characteristic feature of attenuation in their pathogenicity, compared to the parental strain. Comparative in vitro experiments on the immune response and immunostimulating capacity of Y. pseudotuberculosis mutant strains verify their preserved immunogenic potential, predominantly in case of yopK. Hyperplasia and strong activation of the lymph tissue of Peyer's patches, mesenterial lymph nodes, tonsils and spleen of pigs challenged with both mutant strains were proved as immunomorphological rearrangements. The results obtained give the reason to claim that the genetically constructed yopK null mutant strain is significantly attenuated but is still immunogenic and has the potential for a live vaccine carrier strain.
|
|
| 11. |
- Sarimov, R, et al.
(författare)
-
Nonthermal GSM microwaves affect chromatin conformation in human lymphocytes similar to heat shock
- 2004
-
Ingår i: IEEE Transactions on Plasma Science. - 0093-3813. ; 32:4, s. 1600-1608
-
Tidskriftsartikel (refereegranskat)abstract
- Here we investigated whether microwaves (MWs) of Global System for Mobile Communication (GSM) induce changes in chromatin conformation in human lymphocytes. Effects of MWs were studied at different frequencies in the range of 895-915 MHz in experiments with lymphocytes from seven healthy persons. Exposure was performed in transverse electromagnetic transmission line cell (TEM-cell) using a GSM test-mobile phone. All standard modulations included 2 W output power in the pulses, specific absorbed rate (SAR) being 5.4 mW/kg. Changes in chromatin conformation, which are indicative of stress response and genotoxic effects, were measured by the method of anomalous viscosity time dependencies (AVTD). Heat shock and treatment with the genotoxic agent camptothecin, were used as positive controls. 30-min exposure to MWs at 900 and 905 MHz resulted in statistically significant condensation of chromatin in lymphocytes from 1 of 3 tested donors. This condensation was similar to effects. of heat shock within the temperature window of 40degreesC-44degreesC. Analysis of pooled data from all donors showed statistically significant effect of 30-min exposure to MWs. Stronger effects of MWs was found following I-h exposure. In replicated experiments, cells from four out of five donors responded to 905 MHz. Responses to 915 MHz were observed in cells from I out of 5 donors, p < 0.002. Dependent on donor, condensation, 3 donors, or decondensation, 1 donor, of chromatin was found in response to I-h exposure. Analysis of pooled data from all donors showed statistically significant effect of 1-h exposure to MWs. In cells from one donor, this effect was frequency-dependent (p < 0.01). Effects of MWs correlated statistically significantly with effects of heat shock and initial state of chromatin before exposure. MWs at 895 and 915 MHz affected chromatin conformation in transformed lymphocytes. The conclusion-GSM microwaves under specific conditions of exposure affected human lymphocytes similar to stress response. The data suggested that the MW effects differ at various GSM frequencies and vary between donors.
|
|
| 12. |
|
|
| 13. |
|
|
