| 1. |
- Ahmadpour, Doryaneh, 1973, et al.
(författare)
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Robustness analysis of HOG pathway genes in Saccharomyces cerevisiae
- 2006
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Ingår i: YSBN Meeting Nov. 14-16, 2006- Vienna- Austria.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Robustness analysis of HOG pathway genes in Saccharomyces cerevisiae Doryaneh Ahmadpour1, Lars-Göran Ottosson1, Markus Krantz2, Jonas Warringer1, Anders Blomberg1 and Stefan Hohmann1* 1Department of Cell and Molecular Biology/Microbiology, Göteborg University, S-405 30 Göteborg, Sweden 2 The Systems Biology Institute (SBI), Shibuya, Tokyo, Japan E-mail: doryaneh.ahmadpour@gmm.gu.se Robustness is a fundamental property of biological systems and crucial for their effective function under internal or external perturbations. For instance, it has been proposed that internal parameters such as gene expression have been optimized during evolution such that a given system has the observed robustness. The permissible ranges of internal parameters in the cells are not comprehensively understood since there has not been a technique to measure such parameters. “Genetic tug-of-war” (gTOW) [1] is a genetic screening method that allows the investigation of the upper limit copy number of genes, and thereby the upper permissible range of gene expression level. This method is based on a 2-micron plasmid vector containing the leu2d allele with a very weak complementation activity and the gene of interest inserted as target gene. When the leu2ura3 deletion yeast cells transformed with pTOW plasmid are cultured under leucine-limiting conditions, there will be a bias toward increasing the plasmid copy number to compensate for the lack of leucine. On the other hand there will be an opposing bias toward decreasing the plasmid copy number if the target gene inhibits growth or has a toxic effect when a certain copy number is exceeded (it reaches to its upper limit). Eventually as a result of the “tug-of-war” between these two selection biases cells with optimized plasmid copy number will be concentrated. In this study we have applied the gTOW method on 29 HOG pathway related genes in Saccharomyces cerevisiae. The high osmolarity glycerol (HOG) MAPK pathway is essential for yeast survival in high osmolarity condition and consists of two branches that activate a MAPK (Hog1) via a MAPKK (Pbs2) to orchestrate part of the transcriptional response. The HOG pathway is the best understood osmoresponsive system in eukaryotes and the quantitative data provided by the gTOW method collating with the existing computational models could be used to analyze the robustness and fragility of the pathway. 1. Hisao Moriya, Yuki Shimizu-Yoshida and Hiroaki Kitano, 2006, PLoS Genetics, 2:7
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| 2. |
- Ahmadpour, Doryaneh, 1973, et al.
(författare)
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Robustness analysis of HOG pathway related genes in Saccharomyces cerevisiae
- 2007
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Ingår i: FEBS-SysBio March 10-16, 2007- Gosau, Austria.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Robustness analysis of HOG pathway related genes in Saccharomyces cerevisiae Doryaneh Ahmadpour1, Lars-Göran Ottosson1, Markus Krantz2, Jonas Warringer1, Anders Blomberg1 and Stefan Hohmann1* 1Department of Cell and Molecular Biology/Microbiology, Göteborg University, S-405 30 Göteborg, Sweden 2 The Systems Biology Institute (SBI), Shibuya, Tokyo, Japan E-mail: doryaneh.ahmadpour@gmm.gu.se Robustness is a fundamental property of biological systems and crucial for their effective function under internal or external perturbations. For instance, it has been proposed that internal parameters such as gene expression have been optimized during evolution such that a given system has the observed robustness. The permissible ranges of internal parameters in the cells are not comprehensively understood since there has not been a technique to measure such parameters. “Genetic tug-of-war” (gTOW) [1] is a genetic screening approach that allows the determination of the upper limit copy number of genes, and thereby the upper permissible range of the level of gene expression. This method is based on a 2-micron plasmid vector containing the LEU2d allele with a very weak complementation activity and the gene of interest inserted as target gene. When the leu2 ura3 mutant yeast transformed with pTOW plasmids is cultured under leucine-limiting conditions, there will be a bias toward increasing the plasmid copy number to satisfy the requirement for leucine. On the other hand there will be an opposing bias toward decreasing the plasmid copy number if the target gene inhibits growth when a certain copy number is exceeded (i.e. it reaches its upper limit). Eventually as a result of the “tug-of-war” between these two selection biases cells with optimized plasmid copy number will accumulate. In this study we have applied the gTOW method on 29 HOG pathway genes in S. cerevisiae. The high osmolarity glycerol (HOG) MAPK pathway is essential for yeast survival in high osmolarity condition [2]. It consists of two branches that activate a MAPK (Hog1) to orchestrate part of the transcriptional response. The HOG pathway is the best understood osmoresponsive system in eukaryotes. The quantitative data provided by the gTOW method collating with the existing computational models [3] could be used to analyze the robustness and fragility of the pathway. 1. Moriya H, et al., (2006), PLoS Genet 2(7): e111 2. Hohmann S (2002), Microbiol Mol Biol Rev 66:300 3. Klipp E, et al., (2005), Nat Biotechnol 23:975
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| 3. |
- Andersson, Lisa, et al.
(författare)
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Investigating opioid-related fatalities in southern Sweden : contact with care-providing authorities and comparison of substances
- 2020
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Ingår i: Harm Reduction Journal. - : Springer Science and Business Media LLC. - 1477-7517. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Opioid-related deaths have increased in Western countries over recent decades. Despite numerous studies investigating opioid-related mortality, only a few have focused on the lives of the deceased individuals prior to their deaths, specifically regarding contact with care-providing authorities such as health, social and correctional services. Furthermore, a change has been noted in the last two decades as to which opioids cause most deaths, from heroin to prescription opioids. However, studies comparing fatalities caused by different substances are rare. The aim of this study was to investigate contact with care-providing authorities during the year prior to death among individuals who died as a result of opioid intoxication and to analyse differences relating to which opioids caused their deaths. METHODS: The study is based on retrospective register data and includes 180 individuals with a history of illicit drug use, who died from opioid intoxication in Skåne, Sweden, between 1 January 2012 to 31 December 2013 and 1 July 2014 to 30 June 2016. Intoxications caused by heroin, methadone, buprenorphine and fentanyl were included. Data were collected from the National Board of Forensic Medicine, regional health care services, municipal social services and the Prison and Probation Service. Statistical testing was performed using Pearson's chi-square test, Fisher's exact test and the Mann-Whitney U test to analyse group differences. RESULTS: A total of 89% of the deceased individuals had been in contact with one or more of the care-providing authorities during the year prior to death; 75% had been in contact with health care, 69% with the social services, 28% with the Prison and Probation Service, and 23% had been enrolled in opioid substitution treatment at some point during their final year of life. Few differences appeared between the substance groups with regard to which opioid contributed to the death. In addition to opioids, sedatives were present in more than 80% of the cases. Individuals whose deaths were buprenorphine-related had been in contact with the social services to a significantly lesser extent during the year prior to death. CONCLUSIONS: The studied population is characterised by extensive contact with care-providing authorities, thus providing numerous opportunities for authorities to reach this group with preventive and other interventions. Few differences emerged between groups with regard to which opioid had contributed to the death.
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| 4. |
- Babazadeh, Roja, et al.
(författare)
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The Ashbya gossypiiEF-1α promoter of the ubiquitously used MX cassettes is toxic to Saccharomyces cerevisiae.
- 2011
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Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793.
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Tidskriftsartikel (refereegranskat)abstract
- Protein overexpression based on introduction of multiple gene copies is well established. To improve purification or quantification, proteins are typically fused to peptide tags. In Saccharomyces cerevisiae, this has been hampered by multicopy toxicity of the TAP and GFP cassettes used in the global strain collections. Here, we show that this effect is due to the EF-1α promoter in the HIS3MX marker cassette rather than the tags per se. This promoter is frequently used in heterologous marker cassettes, including HIS3MX, KanMX, NatMX, PatMX and HphMX. Toxicity could be eliminated by promoter replacement or exclusion of the marker cassette. To our knowledge, this is the first report of toxicity caused by introduction of a heterologous promoter alone.
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| 5. |
- Bendroth, Peter, et al.
(författare)
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Comparison of ethyl glucuronide in hair with phosphatidylethanol in whole blood as post-mortem markers of alcohol abuse
- 2008
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Ingår i: Forensic Science International. - : Elsevier BV. - 0379-0738 .- 1872-6283. ; 176:1, s. 76-81
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Tidskriftsartikel (refereegranskat)abstract
- Ethyl glucuronide (EtG) is a direct metabolite of ethanol and has been used as a marker of alcohol abuse in both urine and hair. This study investigated the value of EtG testing in post-mortem hair for diagnostic improvement of alcohol abuse in forensic medicine. Material from 70 consecutive medico-legal autopsies was collected in accordance with the recommendations on ethics by the Swedish National Board of Forensic Medicine. A method for determination of EtG in hair samples was developed using ultra performance liquid chromatography/electrospray tandem mass spectrometry (UPLC/ESI-MS/MS; LOQ, 2.5 pg/mg). The result of the EtG analysis was compared with the findings of phosphatidylethanol (PEth) in femoral whole blood, as measured by high performance liquid chromatography with an evaporative light-scattering detector (HPLC–ELSD; LOQ, 0.22 μmol/l). Evaluation of liver histology and anamnestic evidence of alcohol abuse of the deceased were taken in consideration for the interpretation. Measurable levels of EtG were present in 49 of the 70 autopsy cases whereas PEth was present in 36. Thirty-nine cases had EtG levels above the cutoff limit (≥30 pg/mg) compared with 29 for PEth (≥0.7 μmol/l). Fifteen cases had EtG as exclusive indicator for alcohol abuse compared with four cases for PEth. These findings suggest that measurements of EtG in hair may provide improved diagnostic information on alcohol abuse, due to a long retrospective time-window for detection and stability of EtG in hair in the decaying cadaver. However, an EtG level below the cutoff does not completely exclude previous alcohol abuse.
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| 6. |
- Blomquist, Axel, et al.
(författare)
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Persistent Aspergillus fumigatus infection in cystic fibrosis : impact on lung function and role of treatment of asymptomatic colonization-a registry-based case-control study
- 2022
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Ingår i: BMC Pulmonary Medicine. - : Springer Science and Business Media LLC. - 1471-2466. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Aspergillus fumigatus is the most common filamentous fungus isolated from the airways of people with cystic fibrosis (CF). The aim of this study was to investigate how chronic A. fumigatus colonization affects lung function in people with CF, to identify risk factors for colonization, and to evaluate antifungal treatment of asymptomatic Aspergillus colonization.METHODS: Data from 2014-2018 was collected from the Swedish CF registry and medical records. Baseline data before the start of A. fumigatus colonization was compared with the two succeeding years to evaluate how colonization and treatment affected lung function and other clinical aspects.RESULTS: A total of 437 patients were included, of which 64 (14.6%) became colonized with A. fumigatus during the study period. Inhaled antibiotics was associated with A. fumigatus colonization (adjusted OR 3.1, 95% CI 1.6-5.9, p < 0.05). Fungal colonization was not associated with a more rapid lung function decline or increased use of IV-antibiotics compared to the non-colonized group, but patients with A. fumigatus had more hospital days, a higher increase of total IgE, and higher eosinophil counts. In the Aspergillus group, 42 patients were considered to be asymptomatic. Of these, 19 patients received antifungal treatment. Over the follow up period, the treated group had a more pronounced decrease in percent predicted Forced Expiratory Volume in one second (ppFEV1) compared to untreated patients (- 8.7 vs - 1.4 percentage points, p < 0.05).CONCLUSION: Inhaled antibiotics was associated with A. fumigatus colonization, but no association was found between persistent A. fumigatus and subsequent lung function decline. No obvious benefits of treating asymptomatic A. fumigatus colonization were demonstrated.
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| 7. |
- Cvijovic, Marija, 1977, et al.
(författare)
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Strategies for structuring interdisciplinary education in systems biology: An European perspective
- 2016
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Ingår i: npj Systems Biology and Applications. - : Springer Science and Business Media LLC. - 2056-7189. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Systems Biology is an approach to biology and medicine that has the potential to lead to a better understanding of how biological properties emerge from the interaction of genes, proteins, molecules, cells and organisms. The approach aims at elucidating how these interactions govern biological function by employing experimental data, mathematical models and computational simulations. As Systems Biology is inherently multidisciplinary, education within this field meets numerous hurdles including departmental barriers, availability of all required expertise locally, appropriate teaching material and example curricula. As university education at the Bachelor’s level is traditionally built upon disciplinary degrees, we believe that the most effective way to implement education in Systems Biology would be at the Master’s level, as it offers a more flexible framework. Our team of experts and active performers of Systems Biology education suggest here (i) a definition of the skills that students should acquire within a Master’s programme in Systems Biology, (ii) a possible basic educational curriculum with flexibility to adjust to different application areas and local research strengths, (iii) a description of possible career paths for students who undergo such an education, (iv) conditions that should improve the recruitment of students to such programmes and (v) mechanisms for collaboration and excellence spreading among education professionals. With the growing interest of industry in applying Systems Biology approaches in their fields, a concerted action between academia and industry is needed to build this expertise. Here we present a reflection of the European situation and expertise, where most of the challenges we discuss are universal, anticipating that our suggestions will be useful internationally. We believe that one of the overriding goals of any Systems Biology education should be a student’s ability to phrase and communicate research questions in such a manner that they can be solved by the integration of experiments and modelling, as well as to communicate and collaborate productively across different experimental and theoretical disciplines in research and development.
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| 8. |
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| 9. |
- Hovelius, Lennart, et al.
(författare)
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Non-operative treatment of primary anterior shoulder dislocation in patients forty years of age and younger : a prospective twenty-five-year follow-up
- 2008
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Ingår i: Journal of Bone and Joint Surgery. American volume. - : Journal of Bone and Joint Surgery. - 0021-9355 .- 1535-1386. ; 90:5, s. 945-952
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Tidskriftsartikel (refereegranskat)abstract
- Background: During 1978 and 1979, we initiated a prospective multicenter study to evaluate the results of nonoperative treatment of primary anterior shoulder dislocation. In the current report, we present the outcome after twenty-five years.Methods: Two hundred and fifty-five patients (257 shoulders) with an age of twelve to forty years who had a primary anterior shoulder dislocation were managed with immobilization (achieved by tying the arm to the torso with use of a bandage) or without immobilization. All 227 living patients (229 shoulders) completed the follow-up questionnaire, and 214 patients completed the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire.Results: Ninety-nine (43%) of 229 shoulders had not redislocated, and seventeen (7%) redislocated once. Thirty-three recurrent dislocations had become stable over time (14.4%), and eighteen were considered to be still recurrent (7.9%). Sixty-two shoulders (27%) had undergone surgery for the treatment of recurrent instability. Immobilization after the primary dislocation did not change the prognosis. Only two of twenty-four shoulders with a fracture of the greater tuberosity at the time of the primary dislocation redislocated (p < 0.001). When shoulders with a fracture of the greater tuberosity were excluded, forty-four (38%) of 115 shoulders in patients who had been twelve to twenty-five years of age at the time of the original dislocation and sixteen (18%) of ninety shoulders in patients who had been twenty-six to forty years of age had undergone surgical stabilization. At twenty-five years, fourteen (23%) of sixty-two shoulders that had undergone surgical stabilization were in patients who subsequently had a contralateral dislocation, compared with seven (7%) of ninety-nine shoulders in patients in whom the index dislocation had been classified as solitary (p = 0.01). Gender and athletic activity did not appear to affect the redislocation rate; however, women had worse DASH scores than men did (p = 0.006).Conclusions: After twenty-five years, half of the primary anterior shoulder dislocations that had been treated nonoperatively in patients with an age of twelve to twenty-five years had not recurred or had become stable over time.Level of Evidence: Prognostic Level I. See Instructions to Authors for a complete description of levels of evidence.
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| 10. |
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