| 1. |
|
|
| 2. |
- Karlsson, Jens
(författare)
-
Breakthrough in Chinese Kant Scholarship : Interview with Prof. Deng Xiaomang
- 2021
-
Ingår i: Kantian journal. - : Immanuel Kant Baltic Federal University. - 0207-6918 .- 2310-3701. ; 40:2, s. 131-150
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Prof. Deng Xiaomang’s translations of the Critique of the Power of Judgment (2002), the Critique of Practical Reason (2003), and the Critique of Pure Reason (2004), were the first Chinese editions of Kant’s three Critiques translated in their entirety from the German originals. This interview tracks his scholarship, placing it within the broader scope of historical and contemporary Kant scholarship in China. Among the topics addressed, the reception of Kantian philosophy among the so called “New Confucians”, as well as the utility of Kantian thought as a tool for the reformation of traditional Confucian culture, are given considerable attention. Professor Deng also shares some thoughts on the process of translating classical German philosophical texts into Chinese and provides an overview of his scholarship as a translator and thinker.
|
|
| 3. |
- Karlsson, Jens
(författare)
-
Hfq- and sRNA-mediated regulation in Neisseria meningitidis
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neisseria meningitidis, also known as the meningococcus, is a human-specific pathogen that commonly colonises the nasopharynx without causing disease. For reasons unknown, N. meningitidis can traverse the nasopharyngeal epithelium and enter the bloodstream, causing invasive meningococcal disease manifesting in septicaemia and/or meningitis. Meningococci are divided into serogroups based on the serological response to their different polysaccharide capsule. They can also be subdivided into clonal complexes based on multi locus sequence typing of seven housekeeping genes. An interesting feature of N. meningitidis is the compact genome with frequent numbers of repeat elements present throughout the genome. DNA uptake sequences, repeat sequences, neisserial intergenic mosaic elements, Correia repeat enclosed elements, tandem repeats and insertion sequences are all examples of such repeat elements. The presence of these repeat sequence elements is attributed to the great genome flexibility that N. meningitidis possess. Repeat sequence and genome flexibility allows meningococci to switch gene expression in an ON/OFF manner as well as acquiring new genetic elements beneficial to the bacterium. N. meningitidis utilises several virulence factors in its arsenal to overcome the host immune system. Polysaccharide capsule shields the bacterium from a variety of antimicrobial agents and complement system. Capsule can also prevent opsonophagocytosis as well as cover protein epitopes targeted by antibodies. Type IV pilus is another virulence factor that facilitate twitching motility, enables uptake of exogenous DNA, and adhesion to both bacteria and host cells. N. meningitidis is a human-specific bacteria in part due to the bacterium having specialised in acquiring iron from human iron sequestering proteins such as transferrin, lactoferrin, haemoglobin and haemoglobin-haptoglobin. These iron sequestering proteins are all part of the host nutritional immunity, directed to deprive bacteria from essential nutrients. After iron is extracted from human proteins, N. meningitidis utilises an iron transport system to shuttle iron from the outer membrane to the cytoplasm. The protein FbpA is known to perform the iron transport through the periplasm. Recent findings have elucidated the increasing importance of sRNAs as possible mediators for N. meningitidis sudden switch from a passive coloniser to lethal pathogen. The RNA chaperone Hfq is often required for the function of a class of sRNA, called trans-encoded sRNAs, and acts as a matchmaker between sRNA and its target mRNA. There are also Hfq-independent sRNAs, called cis-encoded sRNA, that usually enact their functions on the same transcript in which they are transcribed. The work presented in this thesis aims to further the knowledge of Hfq-dependent and independent sRNAs within N. meningitidis as well as explore Hfq/RNA regulation impact on invasive meningococcal disease. The structure of Hfq as well as two point mutated variants of Hfq have been determined through X ray crystallography. Several RNAs were used to investigate RNA binding patterns in wild-type Hfq in comparison with point mutated variants of Hfq predicted to affect Hfq binding capabilities to RNA species. In this research, a previously Hfq-dependent uncharacterised sRNA, termed NirF, was shown to be a negative regulator of fbpA. NirF is expressed during iron replete conditions and is thought to act in coordination with the iron-responsive transcriptional regulator Fur to prevent possible hazardous intake of excess iron. The studies presented herein continues by investigation of a phenotype in a Hfq knock-out strain of N. meningitidis. The Hfq knock-out strain revealed a visual increase in surface blebbing which at a closer inspection was deemed to be membrane vesicles These vesicles were smaller in size and accounted for a hundred times increased yield when compared to membrane vesicles harvested from the wild-type counterpart. Proteomic analysis revealed similar protein content but with distinct differences. Of note, the membrane vesicles from the Hfq-knock out strain contained fewer numbers of different proteins which resulted in an enrichment of immunogenic proteins such as Opc, PorA, PorB and App. While studying the phenotypic effects of Hfq knock-out in N. meningitidis, an impact on the regulation of iga, the gene encoding the IgA1P protein was discovered. IgA1P is classically known to cleave IgA1 antibodies. Further investigation revealed that a specific type of IgA1P can also cleave IgG3 with the possibility to enhance N. meningitidis survival in the human host. In fact, this additional cleaving type including IgG3 was significantly associated with invasive disease isolates of N. meningitidis in comparison with carrier isolates. The polysaccharide capsule is a vital virulence factor for the development of invasive meningococcal disease. Further research was dedicated to investigating sRNA dependent regulation of capsule production. A previously known RNA thermosensor in the capsule biosynthesis operon was studied for potential variations which could have an impact on capsule regulation. Five novel RNA thermosensor variants were discovered which all resulted in a hypercapsulation phenotype. These new RNA thermosensors, together with previously discovered RNA thermosensors increasing capsule production, were all sufficient to protect N. meningitidis from high exposure to human serum. The abnormal capsule regulation by disrupted RNA thermosensors were significantly associated with invasive meningococcal disease isolates. Furthermore, RNA thermosensor disruption was identified to be the singular feature which significantly differentiated two closely related meningococcal isolates whereas the isolate having the disrupted RNA thermosensor resulted in invasive meningococcal disease. The works included in this thesis show several new features of Hfq-dependent and independent sRNA regulations and the impact on N. meningitidis adaptation to environmental factors and virulence gene expression. Further research is needed to fully understand the triggering switch between meningococcal colonisation and pathogenesis, but the work included herein has contributed to one step closer to this goal.
|
|
| 4. |
- Gaudenzi, Giulia, et al.
(författare)
-
Point-of-Care Approaches for Meningitis Diagnosis in a Low-Resource Setting (Southwestern Uganda) : Observational Cohort Study Protocol of the "PI-POC" Trial
- 2020
-
Ingår i: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 22:11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A timely differential diagnostic is essential to identify the etiology of central nervous system (CNS) infections in children, in order to facilitate targeted treatment, manage patients, and improve clinical outcome. Objective: The Pediatric Infection-Point-of-Care (PI-POC) trial is investigating novel methods to improve and strengthen the differential diagnostics of suspected childhood CNS infections in low-income health systems such as those in Southwestern Uganda. This will be achieved by evaluating (1) a novel DNA-based diagnostic assay for CNS infections, (2) a commercially available multiplex PCR-based meningitis/encephalitis (ME) panel for clinical use in a facility-limited laboratory setting, (3) proteomics profiling of blood from children with severe CNS infection as compared to outpatient controls with fever yet not severely ill, and (4) Myxovirus resistance protein A (MxA) as a biomarker in blood for viral CNS infection. Further changes in the etiology of childhood CNS infections after the introduction of the pneumococcal conjugate vaccine against Streptococcus pneumoniae will be investigated. In addition, the carriage and invasive rate of Neisseria meningitidis will be recorded and serotyped, and the expression of its major virulence factor (polysaccharide capsule) will be investigated. Methods: The PI-POC trial is a prospective observational study of children including newborns up to 12 years of age with clinical features of CNS infection, and age-/sex-matched outpatient controls with fever yet not severely ill. Participants are recruited at 2 Pediatric clinics in Mbarara, Uganda. Cerebrospinal fluid (for cases only), blood, and nasopharyngeal (NP) swabs (for both cases and controls) sampled at both clinics are analyzed at the Epicentre Research Laboratory through gold-standard methods for CNS infection diagnosis (microscopy, biochemistry, and culture) and a commercially available ME panel for multiplex PCR analyses of the cerebrospinal fluid. An additional blood sample from cases is collected on day 3 after admission. After initial clinical analyses in Mbarara, samples will be transported to Stockholm, Sweden for (1) validation analyses of a novel nucleic acid-based POC test, (2) biomarker research, and (3) serotyping and molecular characterization of S. pneumoniae and N. meningitidis. Results: A pilot study was performed from January to April 2019. The PI-POC trial enrollment of patients begun in April 2019 and will continue until September 2020, to include up to 300 cases and controls. Preliminary results from the PI-POC study are expected by the end of 2020. Conclusions: The findings from the PI-POC study can potentially facilitate rapid etiological diagnosis of CNS infections in low-resource settings and allow for novel methods for determination of the severity of CNS infection in such environment.
|
|
| 5. |
|
|
| 6. |
- Karlsson, Jens
(författare)
-
Kinas migrerande bondearbetare
- 2020
-
Ingår i: Orientaliska Studier. - 0345-8997. ; :163, s. 6-14
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 7. |
- Karlsson, Jens
(författare)
-
Kinesisk arbetardiktning då och nu
- 2020
-
Ingår i: Orientaliska Studier. - 0345-8997. ; :163, s. 15-26
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 8. |
- Karlsson, Jens, et al.
(författare)
-
Novel hypercapsulation RNA thermosensor variants in Neisseria meningitidis and their association with invasive meningococcal disease : a genetic and phenotypic investigation and molecular epidemiological study
- 2020
-
Ingår i: The Lancet Microbe. - : Elsevier. - 2666-5247. ; 1:8, s. E319-E327
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Neisseria meningitidis is the causative agent of invasive meningococcal disease and the polysaccharide capsule is one of its major virulence factors. Biosynthesis of the meningococcal capsule is controlled by an RNA thermosensor (RNAT) in the 5'-untranslated region (5'-UTR) of the cssA gene. The function of the RNAT depends on an 8-bp tandem repeat configuration. We aimed to identify and characterise novel RNATs in meningococcal isolates responsible for regulating capsule production.Methods: We investigated the allele igr_up_NEIS0055, containing the 5'-UTR of the cssA gene, in clinical meningococcal isolates for which whole-genome sequences are available on the Neisseria PubMLST database and that were isolated in Europe between Jan 1, 2010, and Dec 31, 2018. Eight isolates with different RNAT tandem repeat configurations were selected for genetic and phenotypic studies. The thermosensing capability of the RNAT and capsule production was tested with immunoblots. Bacterial survival by capsule protection was assessed with a human serum stress assay and capsule interference with bacterial cell adhesion was evaluated with a bacterial adhesion assay. The dataset of RNAT configurations was analysed for an association with invasive meningococcal disease, and was stratified to visualise the distribution of RNAT configurations within the meningococcal population.Findings: Our search of PubMLST identified 112 alleles for the igr_up_NEIS0055 locus and 7013 N meningitidis isolates. Five novel RNAT tandem repeat configurations were identified and eight RNAT tandem repeat configurations, ranging from 1 x 8-bp up to 8 x 8-bp, were characterised. The disrupted RNATs (1 x 8-bp and 3 x 8-bp to 8 x 8-bp) confer upregulated CssA expression and increased capsule production compared with the native 2 x 8-bp configuration, resulting in a hypercapsulation phenotype. Increased capsule production was associated with higher survival rates in up to 25% human serum. The prevalence of a disrupted RNAT resulting in hypercapsulation was almost twice as high in invasive meningococcal disease isolates compared with carrier isolates. Disrupted RNATs were especially attributed to isolates of capsule group B and C, and clonal complexes 23, 32, 213, and 269. Hypercapsulation in one isolate led to lower adhesion onto pharyngeal cells compared with a similar isolate with low capsule production.Interpretation: Six non-canonical RNAT tandem repeat variants (3 x 8-bp to 8 x 8-bp) were identified in the igr_up_NEIS0055 locus of N meningitidis that induce a hypercapsulation phenotype, thus providing the meningococci with better protection against host complement-mediated killing than does the native RNAT (2 x 8-bp). Further research is warranted to strengthen the association between hypercapsulation and the progression of invasive meningococcal disease, and to investigate the role of regulatory RNAs in meningococcal virulence and as potential markers for disease progression.
|
|
| 9. |
|
|
| 10. |
- Arvidsson, Björn L, 1952-, et al.
(författare)
-
Recruitment of the threatened mussel Margaritifera margaritifera in relation to mussel population size, mussel density and host density
- 2012
-
Ingår i: Aquatic conservation. - Malden, MA : John Wiley & Sons. - 1052-7613 .- 1099-0755. ; 22, s. 526-532
-
Tidskriftsartikel (refereegranskat)abstract
- Anthropogenic, abiotic factors are considered main causes of recruitment failure of unionid mussels, including the freshwater pearl mussel (Margaritifera margaritifera). In this large-scale investigation, we instead examined the relationship between biotic factors and mussel recruitment.Juvenile mussel density was positively related to both mussel population size and density of which the last appeared to be a more accurate measure of recruitment.Host fish density of young-of-the-year and older brown trout (Salmo trutta) were positively related to recruitment. Moreover, the mean density of both age classes of fish, when grouped into density classes was positively related to juvenile mussel density, an effect that decreased at trout densities above 10 trout 100 m-2.There was a higher relative importance of mussel population size and density than trout density to recruitment.To increase recruitment of juvenile mussels, managers may apply measures that increase mussel density, and trout density up to about 10 trout 100 m-2 in connection to mussel beds. Mussel beds may also be managed and one possible measure within small and sparse mussel populations may be to concentrate the remaining mussels to areas where trout density is high. Likewise, young-of-the-year trout may also be moved to areas of high mussel density, as young trout individuals are relatively resident during their first year. This may increase mussel larval infection rates and mussel recruitment.
|
|
