| 1. |
- Fan, Xuelong, et al.
(författare)
-
Effects of sensor types and angular velocity computational methods in field measurements of occupational upper arm and trunk postures and movements
- 2021
-
Ingår i: Sensors. - : MDPI AG. - 1424-8220. ; 21:16
-
Tidskriftsartikel (refereegranskat)abstract
- Accelerometer-based inclinometers have dominated kinematic measurements in previous field studies, while the use of inertial measurement units that additionally include gyroscopes is rapidly increasing. Recent laboratory studies suggest that these two sensor types and the two commonly used angular velocity computational methods may produce substantially different results. The aim of this study was, therefore, to evaluate the effects of sensor types and angular velocity computational methods on the measures of work postures and movements in a real occupational setting. Half-workday recordings of arm and trunk postures, and movements from 38 warehouse workers were compared using two sensor types: accelerometers versus accelerometers with gyroscopes—and using two angular velocity computational methods, i.e., inclination velocity versus generalized velocity. The results showed an overall small difference (<2° and value independent) for posture percentiles between the two sensor types, but substantial differences in movement percentiles both between the sensor types and between the angular computational methods. For example, the group mean of the 50th percentiles were for accelerometers: 71°/s (generalized velocity) and 33°/s (inclination velocity)—and for accelerometers with gyroscopes: 31°/s (generalized velocity) and 16°/s (inclination velocity). The significant effects of sensor types and angular computational methods on angular velocity measures in field work are important in inter-study comparisons and in comparisons to recommended threshold limit values.
|
|
| 2. |
- Forsman, Mikael, Professor, et al.
(författare)
-
Mind the gap – development of conversion models between accelerometer- and IMU-based measurements of arm and trunk postures and movements in warehouse work
- 2022
-
Ingår i: Applied Ergonomics. - : Elsevier BV. - 0003-6870 .- 1872-9126. ; 105
-
Tidskriftsartikel (refereegranskat)abstract
- Sensor type (accelerometers only versus inertial measurement units, IMUs) and angular velocity computational method (inclination versus generalized velocity) have been shown to affect the measurements of arm and trunk movements. This study developed models for conversions between accelerometer and IMU measurements of arm and trunk inclination and between accelerometer and IMU measurements of inclination and generalized (arm) velocities. Full-workday recordings from accelerometers and IMUs of arm and trunk postures and movements from 38 warehouse workers were used to develop 4 angular (posture) and 24 angular velocity (movement) conversion models for the distributions of the data. A power function with one coefficient and one exponent was used, and it correlated well (r2 > 0.999) in all cases to the average curves comparing one measurement with another. These conversion models facilitate the comparison and merging of measurements of arm and trunk movements collected using the two sensor types and the two computational methods.
|
|
| 3. |
- Negrea, Aurel, et al.
(författare)
-
Salicylidene Acylhydrazides That Affect Type III Protein Secretion in Salmonella enterica Serovar Typhimurium
- 2007
-
Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804. ; 51:8, s. 2867-76
-
Tidskriftsartikel (refereegranskat)abstract
- A collection of nine salicylidene acylhydrazide compounds were tested for their ability to inhibit the activity of virulence-associated type III secretion systems (T3SSs) in Salmonella enterica serovar Typhimurium. The compounds strongly affected Salmonella pathogenicity island 1 (SPI1) T3SS-mediated invasion of epithelial cells and in vitro secretion of SPI1 invasion-associated effector proteins. The use of a SPI1 effector ß-lactamase fusion protein implicated intracellular entrapment of the protein construct upon application of a salicylidene acylhydrazide, whereas the use of chromosomal transcriptional gene fusions revealed a compound-mediated transcriptional silencing of SPI1. Salicylidene acylhydrazides also affected intracellular bacterial replication in murine macrophage-like cells and blocked the transport of an epitope-tagged SPI2 effector protein. Two of the compounds significantly inhibited bacterial motility and expression of extracellular flagellin. We conclude that salicylidene acylhydrazides affect bacterial T3SS activity in S. enterica and hence could be used as lead substances when designing specific inhibitors of bacterial T3SSs in order to pharmaceutically intervene with bacterial virulence.
|
|
| 4. |
- Ahmad, Irfan, et al.
(författare)
-
BcsZ inhibits biofilm phenotypes and promotes virulence by blocking cellulose production in Salmonella enterica serovar Typhimurium
- 2016
-
Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 15
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Cellulose, a 1,4 beta-glucan polysaccharide, is produced by a variety of organisms including bacteria. Although the production of cellulose has a high biological, ecological and economical impact, regulatory mechanisms of cellulose biosynthesis are mostly unknown. Family eight cellulases are regularly associated with cellulose biosynthesis operons in bacteria; however, their function is poorly characterized. In this study, we analysed the role of the cellulase BcsZ encoded by the bcsABZC cellulose biosynthesis operon of Salmonella enterica serovar Typhimurium (S. Typhimurium) in biofilm related behavior. We also investigated the involvement of BcsZ in pathogenesis of S. Typhimurium including a murine typhoid fever infection model. Result: In S. Typhimurium, cellulase BcsZ with a putative periplasmic location negatively regulates cellulose biosynthesis. Moreover, as assessed with a non-polar mutant, BcsZ affects cellulose-associated phenotypes such as the rdar biofilm morphotype, cell clumping, biofilm formation, pellicle formation and flagella-dependent motility. Strikingly, although upregulation of cellulose biosynthesis was not observed on agar plate medium at 37 degrees C, BcsZ is required for efficient pathogen-host interaction. Key virulence phenotypes of S. Typhimurium such as invasion of epithelial cells and proliferation in macrophages were positively regulated by BcsZ. Further on, a bcsZ mutant was outcompeted by the wild type in organ colonization in the murine typhoid fever infection model. Selected phenotypes were relieved upon deletion of the cellulose synthase BcsA and/or the central biofilm activator CsgD. Conclusion: Although the protein scaffold has an additional physiological role, our findings indicate that the catalytic activity of BcsZ effectively downregulates CsgD activated cellulose biosynthesis. Repression of cellulose production by BcsZ subsequently enables Salmonella to efficiently colonize the host.
|
|
| 5. |
- Avican, Kemal, et al.
(författare)
-
RNA atlas of human bacterial pathogens uncovers stress dynamics linked to infection
- 2021
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Bacterial processes necessary for adaption to stressful host environments are potential targets for new antimicrobials. Here, we report large-scale transcriptomic analyses of 32 human bacterial pathogens grown under 11 stress conditions mimicking human host environments. The potential relevance of the in vitro stress conditions and responses is supported by comparisons with available in vivo transcriptomes of clinically important pathogens. Calculation of a probability score enables comparative cross-microbial analyses of the stress responses, revealing common and unique regulatory responses to different stresses, as well as overlapping processes participating in different stress responses. We identify conserved and species-specific ‘universal stress responders’, that is, genes showing altered expression in multiple stress conditions. Non-coding RNAs are involved in a substantial proportion of the responses. The data are collected in a freely available, interactive online resource (PATHOgenex).
|
|
| 6. |
- Behra, Phani Rama Krishna
(författare)
-
Comparative genomics of the genus Mycobacterium : Genome evolution, phylogeny and diversity
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The genus Mycobacterium includes more than 190 species, and many cause severe diseases such as tuberculosis and leprosy. According to the "World Health Organization", in year 2019 alone, 10 million people developed TB, and 1.4 million died. TB had been in decline in developed countries, but made its reappearance as an opportunistic pathogen targeting immuno-compromised AIDS victims. Also, non-tuberculosis mycobacteria (NTM) infections have emerged as a major infectious agent in recent times. NTM occupy diverse ecological niches and can be isolated from soil, tap water, and groundwater. This thesis has investigated the Mycobacterium species from a genomic perspective, focusing on the biology of virulence factors, mobile genetic elements, tRNAs, and non-coding RNAs and their evolutionary distribution and possible relationship with phenotypic diversity. As part of this study, we have sequenced 153 mycobacterial genomes, including type strains, environmental samples, isolates from hospital patients, infected fish, and outbreak samples in an animal facility at Uppsala University. We have provided a phylogenetic tree based on 387 (and 56) core genes covering most species (244 genomes) constituting the Mycobacterium genus. The core gene phylogeny resulted in 33 clades. Subsequently, we have covered different clade groups, such as, M. marinum, M. mucogenicum, M. chelonae and M. chlorophenolicum and investigated the NTM clade-specific genome diversity and evolution. Our examination of non-coding genes showed that the total number of tRNA genes per species varies between 42 and 90. Among the species with more than 50 tRNAs, additional tRNA genes are likely acquired through horizontal gene transfer (HGT), as supported by the presence of closely linked HNH endonuclease gene and GOLLD RNA. We have explored the presence of selenocysteine utility and the gene for selenoprotein "formate dehydrogenase" among 244 mycobacterial genomes. For the M. chlorophenolicum clade, we have explored genes with a role in the bioremediation process. Comparative genomics of M. marinum and M. chelonae clade groups suggest new clusters or subspecies. Mutational hotspots are relatively higher in M. marinum compared to that in M. tuberculosis and M. salmoniphilum. Relatively higher number of hotspots in M. marinum is likely related to its ability to occupy different ecological niches. Finally, the thesis uncovered IS elements, phage sequences, plasmids, tRNA, and ncRNA contributing to mycobacterial evolution.
|
|
| 7. |
- Boekel, Jorrit, et al.
(författare)
-
Comparative tissue transcriptomics reveal prompt inter-organ communication in response to local bacterial kidney infection
- 2011
-
Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 12, s. 123-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Mucosal infections elicit inflammatory responses via regulated signaling pathways. Infection outcome depends strongly on early events occurring immediately when bacteria start interacting with cells in the mucosal membrane. Hitherto reported transcription profiles on host-pathogen interactions are strongly biased towards in vitro studies. To detail the local in vivo genetic response to infection, we here profiled host gene expression in a recent experimental model that assures high spatial and temporal control of uropathogenic Escherichia coli (UPEC) infection within the kidney of a live rat. Results: Transcriptional profiling of tissue biopsies from UPEC-infected kidney tissue revealed 59 differentially expressed genes 8 h post-infection. Their relevance for the infection process was supported by a Gene Ontology (GO) analysis. Early differential expression at 3 h and 5 h post-infection was of low statistical significance, which correlated to the low degree of infection. Comparative transcriptomics analysis of the 8 h data set and online available studies of early local infection and inflammation defined a core of 80 genes constituting a "General tissue response to early local bacterial infections". Among these, 25% were annotated as interferon-gamma (IFN-gamma) regulated. Subsequent experimental analyses confirmed a systemic increase of IFN-gamma in rats with an ongoing local kidney infection, correlating to splenic, rather than renal Ifng induction and suggested this inter-organ communication to be mediated by interleukin (IL)-23. The use of comparative transcriptomics allowed expansion of the statistical data handling, whereby relevant data could also be extracted from the 5 h data set. Out of the 31 differentially expressed core genes, some represented specific 5 h responses, illustrating the value of comparative transcriptomics when studying the dynamic nature of gene regulation in response to infections. Conclusion: Our hypothesis-free approach identified components of infection-associated multi-cellular tissue responses and demonstrated how a comparative analysis allows retrieval of relevant information from lower-quality data sets. The data further define marked representation of IFN-gamma responsive genes and a prompt inter-organ communication as a hallmark of an early local tissue response to infection.
|
|
| 8. |
- Butina, Karen, et al.
(författare)
-
Electrochemical sensing of bacteria via secreted redox active compounds using conducting polymers
- 2019
-
Ingår i: Sensors and actuators. B, Chemical. - : Elsevier. - 0925-4005 .- 1873-3077. ; 297
-
Tidskriftsartikel (refereegranskat)abstract
- Bacterial infections and antibiotic resistance represent major global threats to public health. Current diagnostics use culture based assays that are reliable but slow, hence appealing for new rapid methods. Here we describe redox sensing as a novel concept for rapid, label-free detection of bacteria. We utilize a two-electrode poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) based sensor for detection of bacterially secreted redox-active compounds. Using purified redox-active compounds, we show the ability of the sensor to detect and quantify compounds in micromolar concentrations within minutes. When applied for detection and quantification of Salmonella, we show that secreted, low molecular weight redox compounds cause reduction of the PEDOT:PSS electrode. A potential role of redox sensing in infection diagnostics was demonstrated as uropathogenic strains of E. coli., Staphylococcus, Enterococcus, Pseudomonas, Proteus, and Klebsiella spp., major causes of complicated urinary tract infections, were successfully detected in complex media or processed urine. Since numerous bacterial species are capable of extracellular electron transfer, redox sensing may find use as a generic method for bacterial detection with applications in research laboatories, the clinic and industry alike.
|
|
| 9. |
- Del Bel Belluz, Lisa, et al.
(författare)
-
The Typhoid Toxin Promotes Host Survival and the Establishment of a Persistent Asymptomatic Infection
- 2016
-
Ingår i: PLoS Pathogens. - : Public Library Science. - 1553-7366 .- 1553-7374. ; 12:4
-
Tidskriftsartikel (refereegranskat)abstract
- Bacterial genotoxins, produced by several Gram-negative bacteria, induce DNA damage in the target cells. While the responses induced in the host cells have been extensively studied in vitro, the role of these effectors during the course of infection remains poorly characterized. To address this issue, we assessed the effects of the Salmonella enterica genotoxin, known as typhoid toxin, in in vivo models of murine infection. Immunocompetent mice were infected with isogenic S. enterica, serovar Typhimurium (S. Typhimurium) strains, encoding either a functional or an inactive typhoid toxin. The presence of the genotoxic subunit was detected 10 days post-infection in the liver of infected mice. Unexpectedly, its expression promoted the survival of the host, and was associated with a significant reduction of severe enteritis in the early phases of infection. Immunohistochemical and transcriptomic analysis confirmed the toxin-mediated suppression of the intestinal inflammatory response. The presence of a functional typhoid toxin further induced an increased frequency of asymptomatic carriers. Our data indicate that the typhoid toxin DNA damaging activity increases host survival and favours long-term colonization, highlighting a complex cross-talk between infection, DNA damage response and host immune response. These findings may contribute to understand why such effectors have been evolutionary conserved and horizontally transferred among Gram-negative bacteria.
|
|
| 10. |
- Eckert, Johannes A., et al.
(författare)
-
An optotracer-based antibiotic susceptibility test specifically targeting the biofilm lifestyle of Salmonella
- 2022
-
Ingår i: Biofilm. - : Elsevier BV. - 2590-2075. ; 4, s. 100083-
-
Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance is a medical threat of global dimensions. Proper antimicrobial susceptibility testing (AST) for drug development, patient diagnosis and treatment is crucial to counteract ineffective drug use and resistance development. Despite the important role of bacterial biofilms in chronic and device-associated in-fections, the efficacy of antibiotics is determined using planktonic cultures. To address the need for antibiotics targeting bacteria in the biofilm lifestyle, we here present an optotracing-based biofilm-AST using Salmonella as model. Our non-disruptive method enables real-time recording of the extracellular matrix (ECM) components, providing specific detection of the biofilm lifestyle. Biofilm formation prior to antibiotic challenge can thus be confirmed and pre-treatment data collected. By introducing Kirby-Bauer discs, we performed a broad screen of the effects of antibiotics representing multiple classes, and identified compounds with ECM inhibitory as well as promoting effects. These compounds were further tested in agar-based dose-response biofilm-AST assays. By quantifying the ECM based on the amount of curli, and by visualizing the biofilm size and morphology, we achieved new information directly reflecting the treated biofilm. This verified the efficacy of several antibiotics that were effective in eradicating pre-formed biofilms, and it uncovered intriguing possible resistance mecha-nisms initiated in response to treatments. By providing deeper insights into the resistances and susceptibilities of microbes, expanded use of the biofilm-AST will contribute to more effective treatments of infections and reduced resistance development.
|
|
