| 1. |
- Gröning, Remigius, et al.
(author)
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Intravenous immunoglobulin therapy for COVID-19 in immunocompromised patients : A retrospective cohort study
- 2024
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In: International Journal of Infectious Diseases. - : Elsevier. - 1201-9712 .- 1878-3511. ; 144
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Journal article (peer-reviewed)abstract
- Objectives: To investigate the effectiveness of intravenous immunoglobulin (IVIG) as treatment for COVID-19 in immunocompromised patients. Methods: This retrospective study investigated outcomes for immunocompromised, vaccine non-responsive, patients that between September 2022 and April 2023 received IVIG as treatment for COVID-19 in the region of Västerbotten, Sweden. We analyzed clinical data, viral load, and anti-SARS-CoV-2 IgG binding and neutralization levels of patient serum samples and IVIG production batches. Primary and secondary outcomes were clinical cure and viral clearance, respectively.Results: Sixteen patients were analyzed. After a median COVID-19 duration of 4 weeks, a median 60 g IVIG infusion increased SARS-CoV-2 binding and neutralizing antibody levels, with broad in vitro activity against tested variants. The treatment resulted in abrogation of viremia in all patients and general improvement in 15 survivors that all met the primary endpoint. Thirteen patients met the secondary endpoint at follow-up after a median of four months. Two subjects with persistent SARS-CoV-2 carriage relapsed but were successfully retreated with IVIG.Conclusions: Antibodies in IVIG efficiently neutralized several SARS-CoV-2 variants. Treatment with IVIG was associated with clinical cure and viral clearance in immunocompromised patients. Our data suggests that IVIG could be a novel treatment alternative for COVID-19 for this patient category.
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| 2. |
- Orikiiriza, Judy, et al.
(author)
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Lipid response patterns in acute phase paediatric Plasmodium falciparum malaria
- 2017
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In: Metabolomics. - : Springer Science and Business Media LLC. - 1573-3882 .- 1573-3890. ; 13:4
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Journal article (peer-reviewed)abstract
- Introduction: Several studies have observed serum lipid changes during malaria infection in humans. All of them were focused at analysis of lipoproteins, not specific lipid molecules. The aim of our study was to identify novel patterns of lipid species in malaria infected patients using lipidomics profiling, to enhance diagnosis of malaria and to evaluate biochemical pathways activated during parasite infection.Methods: Using a multivariate characterization approach, 60 samples were representatively selected, 20 from each category (mild, severe and controls) of the 690 study participants between age of 0.5–6 years. Lipids from patient’s plasma were extracted with chloroform/methanol mixture and subjected to lipid profiling with application of the LCMS-QTOF method.Results: We observed a structured plasma lipid response among the malaria-infected patients as compared to healthy controls, demonstrated by higher levels of a majority of plasma lipids with the exception of even-chain length lysophosphatidylcholines and triglycerides with lower mass and higher saturation of the fatty acid chains. An inverse lipid profile relationship was observed when plasma lipids were correlated to parasitaemia.Conclusions: This study demonstrates how mapping the full physiological lipid response in plasma from malaria-infected individuals can be used to understand biochemical processes during infection. It also gives insights to how the levels of these molecules relate to acute immune responses.
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| 3. |
- Surowiec, Izabella, et al.
(author)
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Joint and unique multiblock analysis of biological data : multiomics malaria study
- 2019
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In: Faraday discussions. - Cambridge : Royal Society of Chemistry. - 1359-6640 .- 1364-5498. ; 218, s. 268-283
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Journal article (peer-reviewed)abstract
- Modern profiling technologies enable obtaining large amounts of data which can be later used for comprehensive understanding of the studied system. Proper evaluation of such data is challenging, and cannot be faced by bare analysis of separate datasets. Integrated approaches are necessary, because only data integration allows finding correlation trends common for all studied data sets and revealing hidden structures not known a priori. This improves understanding and interpretation of the complex systems. Joint and Unique MultiBlock Analysis (JUMBA) is an analysis method based on the OnPLS-algorithm that decomposes a set of matrices into joint parts containing variation shared with other connected matrices and variation that is unique for each single matrix. Mapping unique variation is important from a data integration perspective, since it certainly cannot be expected that all variation co-varies. In this work we used JUMBA for integrated analysis of lipidomic, metabolomic and oxylipin datasets obtained from profiling of plasma samples from children infected with P. falciparum malaria. P. falciparum is one of the primary contributors to childhood mortality and obstetric complications in the developing world, what makes development of the new diagnostic and prognostic tools, as well as better understanding of the disease, of utmost importance. In presented work JUMBA made it possible to detect already known trends related to disease progression, but also to discover new structures in the data connected to food intake and personal differences in metabolism. By separating the variation in each data set into joint and unique, JUMBA reduced complexity of the analysis, facilitated detection of samples and variables corresponding to specific structures across multiple datasets and by doing this enabled fast interpretation of the studied system. All this makes JUMBA a perfect choice for multiblock analysis of systems biology data.
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| 4. |
- Surowiec, Izabella, et al.
(author)
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Metabolic signature profiling as a diagnostic and prognostic tool in paediatric Plasmodium falciparum malaria
- 2015
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In: Open Forum Infectious Diseases. - : Oxford University Press. - 2328-8957. ; 2:2
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Journal article (peer-reviewed)abstract
- Background: Accuracy in malaria diagnosis and staging is vital in order to reduce mortality and post infectious sequelae. Herein we present a metabolomics approach to diagnostic staging of malaria infection, specifically Plasmodium falciparum infection in children. Methods: A group of 421 patients between six months and six years of age with mild and severe states of malaria with age-matched controls were included in the study, 107, 192 and 122 individuals respectively. A multivariate design was used as basis for representative selection of twenty patients in each category. Patient plasma was subjected to Gas Chromatography-Mass Spectrometry analysis and a full metabolite profile was produced from each patient. In addition, a proof-of-concept model was tested in a Plasmodium berghei in-vivo model where metabolic profiles were discernible over time of infection. Results: A two-component principal component analysis (PCA) revealed that the patients could be separated into disease categories according to metabolite profiles, independently of any clinical information. Furthermore, two sub-groups could be identified in the mild malaria cohort who we believe represent patients with divergent prognoses. Conclusion: Metabolite signature profiling could be used both for decision support in disease staging and prognostication.
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| 5. |
- Surowiec, Izabella, et al.
(author)
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Quantification of run order effect on chromatography : mass spectrometry profiling data
- 2018
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In: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1568, s. 229-234
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Journal article (peer-reviewed)abstract
- Chromatographic systems coupled with mass spectrometry detection are widely used in biological studies investigating how levels of biomolecules respond to different internal and external stimuli. Such changes are normally expected to be of low magnitude and therefore all experimental factors that can influence the analysis need to be understood and minimized. Run order effect is commonly observed and constitutes a major challenge in chromatography-mass spectrometry based profiling studies that needs to be addressed before the biological evaluation of measured data is made. So far there is no established consensus, metric or method that quickly estimates the size of this effect. In this paper we demonstrate how orthogonal projections to latent structures (OPLS®) can be used for objective quantification of the run order effect in profiling studies. The quantification metric is expressed as the amount of variation in the experimental data that is correlated to the run order. One of the primary advantages with this approach is that it provides a fast way of quantifying run-order effect for all detected features, not only internal standards. Results obtained from quantification of run order effect as provided by the OPLS can be used in the evaluation of data normalization, support the optimization of analytical protocols and identification of compounds highly influenced by instrumental drift. The application of OPLS for quantification of run order is demonstrated on experimental data from plasma profiling performed on three analytical platforms: GCMS metabolomics, LCMS metabolomics and LCMS lipidomics.
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| 6. |
- Surowiec, Izabella, et al.
(author)
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The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children
- 2017
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In: Malaria Journal. - : BIOMED CENTRAL LTD. - 1475-2875. ; 16
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Journal article (peer-reviewed)abstract
- Background: Oxylipins and endocannabinoids are low molecular weight bioactive lipids that are crucial for initiation and resolution of inflammation during microbial infections. Metabolic complications in malaria are recognized contributors to severe and fatal malaria, but the impact of malaria infection on the production of small lipid derived signalling molecules is unknown. Knowledge of immunoregulatory patterns of these molecules in malaria is of great value for better understanding of the disease and improvement of treatment regimes, since the action of these classes of molecules is directly connected to the inflammatory response of the organism.Methods: Detection of oxylipins and endocannabinoids from plasma samples from forty children with uncomplicated and severe malaria as well as twenty controls was done after solid phase extraction followed by chromatography mass spectrometry analysis. The stable isotope dilution method was used for compound quantification. Data analysis was done with multivariate (principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA (R)) and univariate approaches (receiver operating characteristic (ROC) curves, t tests, correlation analysis).Results: Forty different oxylipin and thirteen endocannabinoid metabolites were detected in the studied samples, with one oxylipin (thromboxane B2, TXB2) in significantly lower levels and four endocannabinoids (OEA, PEA, DEA and EPEA) at significantly higher levels in infected individuals as compared to controls according to t test analysis with Bonferroni correction. Three oxylipins (13-HODE, 9-HODE and 13-oxo-ODE) were higher in severe compared to uncomplicated malaria cases according to the results from multivariate analysis. Observed changes in oxylipin levels can be connected to activation of cytochrome P450 (CYP) and 5-lipoxygenase (5-LOX) metabolic pathways in malaria infected individuals compared to controls, and related to increased levels of all linoleic acid oxylipins in severe patients compared to uncomplicated ones. The endocannabinoids were extremely responsive to malaria infection with majority of this class of molecules found at higher levels in infected individuals compared to controls.Conclusions: It was possible to detect oxylipin and endocannabinoid molecules that can be potential biomarkers for differentiation between malaria infected individuals and controls and between different classes of malaria. Metabolic pathways that could be targeted towards an adjunctive therapy in the treatment of malaria were also pinpointed.
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| 7. |
- Ahmad, Irma, et al.
(author)
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High prevalence of persistent symptoms and reduced health-related quality of life 6 months after COVID-19
- 2023
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In: Frontiers In Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 11
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Journal article (peer-reviewed)abstract
- BACKGROUND: The long-term sequelae after COVID-19 constitute a challenge to public health and increased knowledge is needed. We investigated the prevalence of self-reported persistent symptoms and reduced health-related quality of life (HRQoL) in relation to functional exercise capacity, 6 months after infection, and explored risk factors for COVID-19 sequalae.METHODS: This was a prospective, multicenter, cohort study including 434 patients. At 6 months, physical exercise capacity was assessed by a 1-minute sit-to-stand test (1MSTST) and persistent symptoms were reported and HRQoL was evaluated through the EuroQol 5-level 5-dimension (EQ-5D-5L) questionnaire. Patients with both persistent symptoms and reduced HRQoL were classified into a new definition of post-acute COVID syndrome, PACS+. Risk factors for developing persistent symptoms, reduced HRQoL and PACS+ were identified by multivariable Poisson regression.RESULTS: Persistent symptoms were experienced by 79% of hospitalized, and 59% of non-hospitalized patients at 6 months. Hospitalized patients had a higher prevalence of self-assessed reduced overall health (28 vs. 12%) and PACS+ (31 vs. 11%). PACS+ was associated with reduced exercise capacity but not with abnormal pulse/desaturation during 1MSTST. Hospitalization was the most important independent risk factor for developing persistent symptoms, reduced overall health and PACS+.CONCLUSION: Persistent symptoms and reduced HRQoL are common among COVID-19 survivors, but abnormal pulse and peripheral saturation during exercise could not distinguish patients with PACS+. Patients with severe infection requiring hospitalization were more likely to develop PACS+, hence these patients should be prioritized for clinical follow-up after COVID-19.
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| 8. |
- Albrecht, Letusa, et al.
(author)
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var gene transcription and PfEMP1 expression in the rosetting and cytoadhesive Plasmodium falciparum clone FCR3S1.2
- 2011
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In: Malaria Journal. - : BioMed Central. - 1475-2875. ; 10
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Journal article (peer-reviewed)abstract
- Background: The pathogenicity of Plasmodium falciparum is in part due to the ability of the parasitized red blood cell (pRBC) to adhere to intra- vascular host cell receptors and serum-proteins. Binding of the pRBC is mediated by Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a large multi-variant molecule encoded by a family of approximate to 60 var genes. Methods: The study of var gene transcription in the parasite clone FCR3S1.2 was performed by semi-quantitative PCR and quantitative PCR (qPCR). The expression of the major PfEMP1 in FCR3S1.2 pRBC was analysed with polyclonal sera in rosette disruption assays and immunofluorecence. Results: Transcripts from var1 (FCR3S1.2(var1); IT4var21) and other var genes were detected by semi-quantitative PCR but results from qPCR showed that one var gene transcript dominated over the others (FCR3S1.2var2; IT4var60). Antibodies raised in rats to the recombinant NTS-DBL1a of var2 produced in E. coli completely and dosedependently disrupted rosettes (approximate to 95% at a dilution of 1/5). The sera reacted with the Maurer's clefts in trophozoite stages (IFA) and to the infected erythrocyte surface (FACS) indicating that FCR3S1.2var2 encodes the dominant PfEMP1 expressed in this parasite. Conclusion: The major transcript in the rosetting model parasite FCR3S1.2 is FCR3S1.2var2 (IT4var60). The results suggest that this gene encodes the PfEMP1-species responsible for the rosetting phenotype of this parasite. The activity of previously raised antibodies to the NTS-DBL1a of FCR3S1.2var1 is likely due to cross-reactivity with NTS-DBL1 alpha of the var2 encoded PfEMP1.
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| 9. |
- Bergström, Sven, et al.
(author)
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Microbiological features distinguishing Lyme disease and relapsing fever spirochetes
- 2018
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In: Wiener Klinische Wochenschrift. - : Springer. - 0043-5325 .- 1613-7671. ; 130:15-16, s. 484-490
-
Journal article (peer-reviewed)abstract
- The recent proposal of splitting the genus Borrelia into two genera in the newly formed family of Borreliaceae, i.aEuroe. Borrelia and Borreliella has motivated us to reflect upon how these organisms has been characterized and differentiated. This article therefore aims to take a closer look on the biology and virulence attributes of the two suggested genera, i.aEuroe. those causing Lyme borreliosis and relapsing fever borreliosis. Both genera have much in common with similar infection biological features. They are both characterized as bacterial zoonoses, transmitted by hematophagous arthropods with almost identical microbiological appearance. Nevertheless, a closer look at the genotypic and phenotypic characteristics clearly reveals several differences that might motivate the suggested split. On the other hand, a change of this well-established classification within the genus Borrelia might impose an economical burden as well as a great confusion in society, including medical and scientific societies as well as the general population.
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| 10. |
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| 11. |
- Berndtsson, Johan, et al.
(author)
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The coordinative functions of flight strips : Air traffic control revisited
- 1999
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In: Proceedings of the international ACM SIGGROUP conference on Supporting group work. - New York, NY, USA : ACM. - 1581130651 ; , s. 101-110
-
Conference paper (peer-reviewed)abstract
- Cooperation in time-critical and physically distributed worksettings, such as air traffic control, requires extensive coordinationbetween the involved actors. For this coordination to beefficient the controllers rely both on the comprehensive use ofrules and procedures, and on artifacts supporting them infollowing these procedures. At the Copenhagen Air TrafficControl Center this coordination is largely carried out throughthe use of a flight plan database system, paper flight strips, anda closed-circuit television system. In relation to the introductionof a new and increasingly automated system in the year 2003 this paper discusses the coordinative functions served bythese three, soon to be replaced, artifacts from a design perspective.Despite the skepticism expressed in previous research,our results show that a further computerization couldbe successful if the coordinative functions the system currentlyfulfills are properly preserved.
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| 12. |
- Björsell, Tove, et al.
(author)
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Risk factors for impaired respiratory function post COVID-19 : A prospective cohort study of nonhospitalized and hospitalized patients
- 2023
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In: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Inc.. - 0954-6820 .- 1365-2796. ; 293:5, s. 600-614
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Severe COVID-19 increases the risk for long-term respiratory impairment, but data after mild COVID-19 are scarce. Our aims were to determine risk factors for reduced respiratory function 3-6 months after COVID-19 infection and to investigate if reduced respiratory function would relate to impairment of exercise performance and breathlessness.METHODS: Patients with COVID-19 were enrolled at the University Hospitals of Umeå and Örebro, and Karlstad Central Hospital, Sweden. Disease severity was defined as mild (nonhospitalized), moderate (hospitalized with or without oxygen treatment), and severe (intensive care). Spirometry, including diffusion capacity (DLCO ), was performed 3-6 months after hospital discharge or study enrollment (for nonhospitalized patients). Breathlessness (defined as ≥1 according to the modified Medical Research Council scale) and functional exercise capacity (1-min sit-to-stand test; 1-MSTST) were assessed.RESULTS: Between April 2020 and May 2021, 337 patients were enrolled in the study. Forced vital capacity and DLCO were significantly lower in patients with severe COVID-19. Among hospitalized patients, 20% had reduced DLCO , versus 4% in nonhospitalized. Breathlessness was found in 40.6% of the participants and was associated with impaired DLCO . A pathological desaturation or heart rate response was observed in 17% of participants during the 1-MSTST. However, this response was not associated with reduced DLCO .CONCLUSION: Reduced DLCO was the major respiratory impairment 3-6 months following COVID-19, with hospitalization as the most important risk factor. The lack of association between impaired DLCO and pathological physiological responses to exertion suggests that these physiological responses are not primarily related to decreased lung function.
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| 13. |
- Cagigi, Alberto, et al.
(author)
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Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination
- 2021
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In: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 6:22
-
Journal article (peer-reviewed)abstract
- Understanding the presence and durability of antibodies against SARS-CoV-2 in the airways is required to provide insights into the ability of individuals to neutralize the virus locally and prevent viral spread. Here, we longitudinally assessed both systemic and airway immune responses upon SARS-CoV-2 infection in a clinically well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity, from asymptomatic infection to fatal disease. In addition, we evaluated how SARS-CoV-2 vaccination influenced the antibody responses in a subset of these individuals during convalescence as compared with naive individuals. Not only systemic but also airway antibody responses correlated with the degree of COVID-19 disease severity. However, although systemic IgG levels were durable for up to 8 months, airway IgG and IgA declined significantly within 3 months. After vaccination, there was an increase in both systemic and airway antibodies, in particular IgG, often exceeding the levels found during acute disease. In contrast, naive individuals showed low airway antibodies after vaccination. In the former COVID-19 patients, airway antibody levels were significantly elevated after the boost vaccination, highlighting the importance of prime and boost vaccinations for previously infected individuals to obtain optimal mucosal protection.
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| 14. |
- Cochoy, Franck, 1964, et al.
(author)
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Bicycles, cyclists and loads: a comparative analysis of cycling practices in Gothenburg and Toulouse
- 2019
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In: Applied Mobilities. - : Informa UK Limited. - 2380-0127 .- 2380-0135. ; 4:1, s. 1-25
-
Journal article (peer-reviewed)abstract
- This article reports on a video-based analysis of bicycling practices in Gothenburg and Toulouse. It is based on actor-network theory, an approach that studies human and non-human entities and their contributions to social action equally. The paper examines bicycles and their interactions with cyclists and loads in the transport of people and goods. Accordingly, this paper presents methodological, theoretical and empirical contributions to the study of bicycle transportation as a possible method for developing sustainable urban environments. This paper also presents an innovative way to study ordinary social practices and describes how these practices shape associated societal issues.
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| 15. |
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| 16. |
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| 17. |
- Cochoy, Franck, et al.
(author)
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Funny bikes: A symmetrical study of urban space, vehicular units and mobility through thevoyeuristic spokesperson of a video-lens
- 2016
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Conference paper (peer-reviewed)abstract
- This paper presents a video analysis of a biker’s practices in Gothenburg and Toulouse. Itshows how bike-rental stations, bikers, bikes and loads interact, in order to seize theforgotten determinants of sustainable urban logistics. Video recording pays as muchattention to the properties of bikes as to the characteristics of people; it takes into accountthe pragmatic and situated dimension and thus allows a generalized symmetry. From there,we submit the collected material to a double treatment. First, quantitative analysis ofobserved bikes - both “sociographic” and “demographic. Second, through a qualitativeethnomethodological analysis of bike rental sequences we see how processes and systemchannel, standardize and reconfigure behavior.To understand the challenges of our method, we present it in analogy with a famous filmequivalent, Michael Haneke's film(s) Funny games. Despite objectives and content are atodds to one another, the Funny games film(s) and our own videos share at least fiveinteresting features. Empirically the our study focus on the possible reconciliation between sustainability objectives and logistical constraints.
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| 18. |
- Elbir, Haitham, et al.
(author)
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Genome Sequence of the Asiatic Species Borrelia persica
- 2014
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In: Genome Announcements. - 2169-8287. ; 2:1
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Journal article (peer-reviewed)abstract
- We report the complete genome sequence of Borrelia persica, the causative agent of tick-borne relapsing fever borreliosis on the Asian continent. Its genome of 1,784,979 bp contains 1,850 open reading frames, three ribosomal RNAs, and 32 tRNAs. One clustered regularly interspaced short palindromic repeat (CRISPR) was detected.
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| 19. |
- Elbir, Haitham, et al.
(author)
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Genome sequence of the relapsing fever borreliosis species Borrelia hispanica
- 2014
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In: Genome Announcements. - : American Society for Microbiology. - 2169-8287. ; 2:1
-
Journal article (peer-reviewed)abstract
- Borrelia hispanica is the etiological pathogen of tick-borne relapsing fever, transmitted to humans by infected Ornithodoros erraticus ticks. Here we present the 1,783,846-bp draft genome sequence, with an average G+C content of 28%. It has 2,140 open reading frames, 3 ribosomal RNAs, and 32 transfer RNAs.
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| 20. |
- Engström, Patrik, et al.
(author)
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A 2-Pyridone-Amide Inhibitor Targets the Glucose Metabolism Pathway of Chlamydia trachomatis
- 2015
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In: mBio. - 2161-2129 .- 2150-7511. ; 6:1
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Journal article (peer-reviewed)abstract
- In a screen for compounds that inhibit infectivity of the obligate intracellular pathogen Chlamydia trachomatis, we identified the 2-pyridone amide KSK120. A fluorescent KSK120 analogue was synthesized and observed to be associated with the C. trachomatis surface, suggesting that its target is bacterial. We isolated KSK120-resistant strains and determined that several resistance mutations are in genes that affect the uptake and use of glucose-6-phosphate (G-6P). Consistent with an effect on G-6P metabolism, treatment with KSK120 blocked glycogen accumulation. Interestingly, KSK120 did not affect Escherichia coli or the host cell. Thus, 2-pyridone amides may represent a class of drugs that can specifically inhibit C. trachomatis infection. IMPORTANCE Chlamydia trachomatis is a bacterial pathogen of humans that causes a common sexually transmitted disease as well as eye infections. It grows only inside cells of its host organism, within a parasitophorous vacuole termed the inclusion. Little is known, however, about what bacterial components and processes are important for C. trachomatis cellular infectivity. Here, by using a visual screen for compounds that affect bacterial distribution within the chlamydial inclusion, we identified the inhibitor KSK120. As hypothesized, the altered bacterial distribution induced by KSK120 correlated with a block in C. trachomatis infectivity. Our data suggest that the compound targets the glucose-6-phosphate (G-6P) metabolism pathway of C. trachomatis, supporting previous indications that G-6P metabolism is critical for C. trachomatis infectivity. Thus, KSK120 may be a useful tool to study chlamydial glucose metabolism and has the potential to be used in the treatment of C. trachomatis infections.
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| 21. |
- Engström, Patrik, 1982-, et al.
(author)
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Mutations in hemG Mediate Resistance to Salicylidene Acylhydrazides, Demonstrating a Novel Link between Protoporphyrinogen Oxidase (HemG) and Chlamydia trachomatis Infectivity
- 2013
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In: Journal of Bacteriology. - Washington DC, USA : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 195:18, s. 4221-4230
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Journal article (peer-reviewed)abstract
- Salicylidene acylhydrazides (SAHs) inhibit the type III secretion system (T3S) of Yersinia and other Gram-negative bacteria. In addition, SAHs restrict the growth and development of Chlamydia species. However, since the inhibition of Chlamydia growth by SAH is suppressed by the addition of excess iron and since SAHs have an iron-chelating capacity, their role as specific T3S inhibitors is unclear. We investigated here whether SAHs exhibit a function on C. trachomatis that goes beyond iron chelation. We found that the iron-saturated SAH INP0341 (IS-INP0341) specifically affects C. trachomatis infectivity with reduced generation of infectious elementary body (EB) progeny. Selection and isolation of spontaneous SAH-resistant mutant strains revealed that mutations in hemG suppressed the reduced infectivity caused by IS-INP0341 treatment. Structural modeling of C. trachomatis HemG predicts that the acquired mutations are located in the active site of the enzyme, suggesting that IS-INP0341 inhibits this domain of HemG and that protoporphyrinogen oxidase (HemG) and heme metabolism are important for C. trachomatis infectivity.
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| 22. |
- Eriksson, Elina, et al.
(author)
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HCI and UN's Sustainable Development Goals : Responsibilities, Barriers and Opportunities
- 2016
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In: NordiCHI '16. - New York, NY, USA : ACM Digital Library. - 9781450347631
-
Conference paper (peer-reviewed)abstract
- Despite increasing interest, Sustainable HCI has been critiqued for doing too little, and perhaps also at times for doing the wrong things. Still, a field like Human-Computer Interaction should aim at being part of transforming our society into a more sustainable one. But how do we do that, and, what are we aiming for?With this workshop, we propose that HCI should start working with the new global Sustainable Development Goals (SDG) that were formally adopted by the UN in September 2015. How can Sustainable HCI be inspired by, and contribute to these goals? What should we in the field of HCI do more of, and what should we perhaps do less of? In what areas should we form partnerships in order to reach the Sustainable Development Goals and with whom should we partner?
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| 23. |
- Fernández, Leyden, et al.
(author)
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Co-PATHOgenex web application for assessing complex stress responses in pathogenic bacteria
- 2024
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In: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 12:1
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Journal article (peer-reviewed)abstract
- Pathogenic bacteria encounter various stressors while residing in the host. They respond through intricate mechanisms of gene expression regulation, ensuring their survival and adaptation. Understanding how bacteria adapt to different stress conditions through regulatory processes of specific genes requires exploring complex transcriptional responses using gene co-expression networks. We employed a large transcriptome data set comprising 32 diverse human bacterial pathogens exposed to the same 11 host-mimicking stress conditions. Using the weighted gene co-expression network analysis algorithm, we generated bacterial gene co-expression networks. By associating modular eigengene expression with specific stress conditions, we identified gene co-expression modules and stress-specific stimulons, including genes with unique expression patterns under specific stress conditions. Suggesting a new potential role of the frm operon in responding to bile stress in enteropathogenic bacteria demonstrates the effectiveness of our approach. We also revealed the regulation of streptolysin S genes, involved in the production, processing, and export of streptolysin S, a toxin responsible for the beta-hemolytic phenotype of group A Streptococcus. In a comparative analysis of stress responses in three Escherichia coli strains from the core transcriptome, we revealed shared and unique expression patterns across the strains, offering insights into convergent and divergent stress responses. To help researchers perform similar analyses, we created the user-friendly web application Co-PATHOgenex. This tool aids in deepening our understanding of bacterial adaptation to stress conditions and in deciphering complex transcriptional responses of bacterial pathogens.IMPORTANCEUnveiling gene co-expression networks in bacterial pathogens has the potential for gaining insights into their adaptive strategies within the host environment. Here, we developed Co-PATHOgenex, an interactive and user-friendly web application that enables users to construct networks from gene co-expressions using custom-defined thresholds (https://avicanlab.shinyapps.io/copathogenex/). The incorporated search functions and visualizations within the tool simplify the usage and facilitate the interpretation of the analysis output. Co-PATHOgenex also includes stress stimulons for various bacterial species, which can help identify gene products not previously associated with a particular stress condition. Unveiling gene co-expression networks in bacterial pathogens has the potential for gaining insights into their adaptive strategies within the host environment. Here, we developed Co-PATHOgenex, an interactive and user-friendly web application that enables users to construct networks from gene co-expressions using custom-defined thresholds (https://avicanlab.shinyapps.io/copathogenex/). The incorporated search functions and visualizations within the tool simplify the usage and facilitate the interpretation of the analysis output. Co-PATHOgenex also includes stress stimulons for various bacterial species, which can help identify gene products not previously associated with a particular stress condition.
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| 24. |
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| 25. |
- Granvik, Christoffer, et al.
(author)
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Olfactory dysfunction as an early predictor for post-COVID condition at 1-year follow-up
- 2024
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In: Brain and Behavior. - : John Wiley & Sons. - 2162-3279. ; 14:6
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Journal article (peer-reviewed)abstract
- Background: Olfactory dysfunction together with neurological and cognitive symptoms are common after COVID-19. We aimed to study whether performance on olfactory and neuropsychological tests following infection predict post-COVID condition (PCC), persisting symptoms, and reduced health-related quality of life.Methods: Both hospitalized (N = 10) and non-hospitalized individuals (N = 56) were enrolled in this prospective cohort study. Participants were evaluated 1–3 months after infection with an olfactory threshold test and neuropsychological tests, which was used as predictors of PCC. A questionnaire outlining persisting symptoms and the validated instrument EuroQol five-dimension five-level for health-related quality of life assessment were used as outcome data 1 year after infection (N = 59). Principal component analysis was used to identify relevant predictors for PCC at 1 year.Results: Objectively assessed olfactory dysfunction at 1–3 months post infection, but not subjective olfactory symptoms, predicted post-COVID condition with reduced health-related quality of life (PCC+) at 1 year. The PCC+ group scored more often below the cut off for mild cognitive impairment on the Montreal Cognitive Assessment (61.5% vs. 21.7%) and higher on the Multidimensional Fatigue Inventory-20, compared to the group without PCC+.Conclusion: Our results indicate that objectively assessed, olfactory dysfunction is a predictor for PCC+. These findings underscore the importance of objective olfactory testing. We propose that olfactory screening in the early post-acute phase of COVID-19 infection might identify individuals that are at higher risk of developing long-term health sequalae.
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