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Article ; Online: Incidence of invasive infections with Group B streptococcus in adults in Norway 1996-2019: a nationwide registry-based case-control study.

Uggen, Elise / Olaisen, Camilla / Lyng, Randi Valsø / Simonsen, Gunnar Skov / Bævre-Jensen, Roar Magne / Gran, Frode Width / Åsvold, Bjørn Olav / Nilsen, Tom Ivar Lund / Damås, Jan Kristian / Afset, Jan Egil

Infection

2024

Abstract: Purpose: Group B streptococcus (GBS) colonizes the gastrointestinal and vaginal mucosa in healthy ...

Abstract	Purpose: Group B streptococcus (GBS) colonizes the gastrointestinal and vaginal mucosa in healthy adults, but has also become an increasing cause of invasive infection. The aims of this study were to describe the incidence and factors associated with the occurrence of invasive GBS disease in adults in Norway. Methods: We performed a nationwide retrospective case-control study of invasive GBS infections during 1996-2019, with two control groups; invasive Group A streptococcal disease (GAS) to control for changes in surveillance and diagnostics, and a second representing the general population. Results: A total of 3710 GBS episodes were identified. The age-standardized incidence rate increased steadily from 1.10 (95% CI 0.80-1.50) in 1996 to 6.70 (95% CI 5.90-7.50) per 100,000 person-years in 2019. The incidence rate had an average annual increase of 6.44% (95% CI 5.12-7.78). Incidence rates of GAS varied considerably, and there was no evidence of a consistent change over the study period. GBS incidence was highest among adults > 60 years of age. Cardiovascular disease, cancer, and diabetes were the most common comorbid conditions. There was a shift in the distribution of capsular serotypes from three dominant types to more equal distribution among the six most common serotypes. Conclusions: The incidence of invasive GBS disease in adults increased significantly from 1996 to 2019. The increasing age of the population with accompanying underlying comorbid conditions might contribute to the increasing burden of invasive GBS disease. Interestingly, type 1 diabetes was also associated with the occurrence of invasive GBS disease.
Language	English
Publishing date	2024-03-14
Publishing country	Germany
Document type	Journal Article
ZDB-ID	185104-4
ISSN	1439-0973 ; 0300-8126 ; 0173-2129
ISSN (online)	1439-0973
ISSN	0300-8126 ; 0173-2129
DOI	10.1007/s15010-024-02210-3
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Article ; Online: Insights into Heterologous Biosynthesis of Arteannuin B and Artemisinin in

Ikram, Nur Kusaira Khairul / Kashkooli, Arman Beyraghdar / Peramuna, Anantha / Krol, Alexander R van der / Bouwmeester, Harro / Simonsen, Henrik Toft

Molecules (Basel, Switzerland)

2019 Volume 24, Issue 21

Abstract: ...

Abstract	:
MeSH term(s)	Artemisia annua/genetics ; Artemisinins/metabolism ; Bryopsida/genetics ; Bryopsida/metabolism ; Plant Proteins/biosynthesis ; Plant Proteins/genetics ; Plants, Genetically Modified/genetics ; Plants, Genetically Modified/metabolism
Chemical Substances	Artemisinins ; Plant Proteins ; arteannuin B (50906-56-4) ; artemisinin (9RMU91N5K2)
Language	English
Publishing date	2019-10-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules24213822
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Article: Characterization of Leishmania (L.) amazonensis oligopeptidase B and its role in macrophage infection

Barbosa, Gustavo Rolim / Marana, Sandro Roberto / Stolf, Beatriz Simonsen

Parasitology. 20222022 Sept. 15, June 15, v. 149, no. 11

2022

Abstract: ... several virulence factors. Oligopeptidase B (OPB) is a serine peptidase present in prokaryotes, some eukaryotes and ...

Abstract	Leishmania spp. are parasitic protozoa that cause leishmaniasis, a disease endemic in 98 countries. Leishmania promastigotes are transmitted by the vector and differentiate into amastigotes within phagocytic cells of the vertebrate host. To survive in multiple and hostile environments, the parasite has several virulence factors. Oligopeptidase B (OPB) is a serine peptidase present in prokaryotes, some eukaryotes and some higher plants. It has been considered a virulence factor in trypanosomatids, but only a few studies, performed with Old World species, analysed its role in Leishmania virulence or infectivity. L. (L.) amazonensis is an important agent of cutaneous leishmaniasis in Brazil. The L. (L.) amazonensis OPB encoding gene has been sequenced and analysed in silico but has never been expressed. In this work, we produced recombinant L. (L.) amazonensis OPB and showed that its pH preferences, Kₘ and inhibition patterns are similar to those reported for L. (L.) major and L. (L.) donovani OPBs. Since Leishmania is known to secrete OPB, we performed in vitro infection assays using the recombinant enzyme. Our results showed that active OPB increased in vitro infection by L. (L.) amazonensis when present before and throughout infection. Our findings suggest that OPB is relevant to L. (L.) amazonensis infection, and that potential drugs acting through OPB will probably be effective for Old and New World Leishmania species. OPB inhibitors may eventually be explored for leishmaniasis chemotherapy.
Keywords	Leishmania ; amastigotes ; computer simulation ; cutaneous leishmaniasis ; drug therapy ; enzymes ; eukaryotic cells ; genes ; macrophages ; pH ; parasites ; parasitology ; prokaryotic cells ; promastigotes ; serine ; vertebrates ; virulence ; Brazil
Language	English
Dates of publication	2022-0615
Size	p. 1411-1418.
Publishing place	Cambridge University Press
Document type	Article
ZDB-ID	207627-5
ISSN	1469-8161 ; 0031-1820
ISSN (online)	1469-8161
ISSN	0031-1820
DOI	10.1017/S0031182022000816
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Lipid nanoparticle-based strategies for extrahepatic delivery of nucleic acid therapies - Challenges and opportunities.

Simonsen, Jens B

Journal of controlled release : official journal of the Controlled Release Society

2024

Abstract: The advent of lipid nanoparticles (LNPs) containing ionizable cationic lipids has enabled the encapsulation, stabilization, and intracellular delivery of nucleic acid payloads, leading to FDA-approved siRNA-based therapy and mRNA-based vaccines. Other ... ...

Abstract	The advent of lipid nanoparticles (LNPs) containing ionizable cationic lipids has enabled the encapsulation, stabilization, and intracellular delivery of nucleic acid payloads, leading to FDA-approved siRNA-based therapy and mRNA-based vaccines. Other nucleic acid-based therapeutic modalities, including protein replacement and CRISPR-mediated gene knockout and editing are being tested in clinical trials, in many cases, for the treatment of liver-related diseases. However, to fully exploit these therapies beyond the liver, improvements in their delivery to extrahepatic targets are needed. Towards this end, both active targeting strategies based on targeting-ligands grafted onto LNPs and passive targeting relying on physicochemical LNP parameters such as surface composition, charge, and size are being evaluated. Often, the latter strategy depends on the interaction of LNPs with blood components, forming what is known as the biomolecular corona. Here, I discuss potential challenges related to current LNP-based targeting strategies and the studies of the biomolecular corona on LNPs. I propose potential solutions to overcome some of these obstacles and present approaches currently being tested in preclinical- and clinical studies, which face fewer biological barriers than traditional organ-targeting approaches.
Language	English
Publishing date	2024-04-13
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2024.04.022
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Article ; Online: Insights into Heterologous Biosynthesis of Arteannuin B and Artemisinin in Physcomitrella patens

Nur Kusaira Khairul Ikram / Arman Beyraghdar Kashkooli / Anantha Peramuna / Alexander R. van der Krol / Harro Bouwmeester / Henrik Toft Simonsen

Molecules, Vol 24, Iss 21, p

2019 Volume 3822

Abstract: ... amorpha-4,11-diene, and also accumulation of a second product, arteannuin B. This demonstrates ...

Abstract	Metabolic engineering is an integrated bioengineering approach, which has made considerable progress in producing terpenoids in plants and fermentable hosts. Here, the full biosynthetic pathway of artemisinin, originating from Artemisia annua , was integrated into the moss Physcomitrella patens . Different combinations of the five artemisinin biosynthesis genes were ectopically expressed in P. patens to study biosynthesis pathway activity, but also to ensure survival of successful transformants. Transformation of the first pathway gene, ADS , into P. patens resulted in the accumulation of the expected metabolite, amorpha-4,11-diene, and also accumulation of a second product, arteannuin B. This demonstrates the presence of endogenous promiscuous enzyme activity, possibly cytochrome P450s, in P. patens . Introduction of three pathway genes, ADS-CYP71AV1-ADH1 or ADS-DBR2-ALDH1 both led to the accumulation of artemisinin, hinting at the presence of one or more endogenous enzymes in P. patens that can complement the partial pathways to full pathway activity. Transgenic P. patens lines containing the different gene combinations produce artemisinin in varying amounts. The pathway gene expression in the transgenic moss lines correlates well with the chemical profile of pathway products. Moreover, expression of the pathway genes resulted in lipid body formation in all transgenic moss lines, suggesting that these may have a function in sequestration of heterologous metabolites. This work thus provides novel insights into the metabolic response of P. patens and its complementation potential for A. annua artemisinin pathway genes. Identification of the related endogenous P. patens genes could contribute to a further successful metabolic engineering of artemisinin biosynthesis, as well as bioengineering of other high-value terpenoids in P. patens .
Keywords	artemisinin ; physcomitrella patens ; sesquiterpenoids ; malaria ; biotechnology ; Organic chemistry ; QD241-441
Subject code	570
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Insights into heterologous biosynthesis of Arteannuin B and artemisinin in physcomitrella patens

Ikram, Nur Kusaira Khairul / Kashkooli, Arman Beyraghdar / Peramuna, Anantha / Van Der Krol, Alexander R. / Bouwmeester, Harro / Simonsen, Henrik Toft

Molecules

2019 Volume 24, Issue 21

Abstract: ... 4,11-diene, and also accumulation of a second product, arteannuin B. This demonstrates the presence ...

Abstract	Metabolic engineering is an integrated bioengineering approach, which has made considerable progress in producing terpenoids in plants and fermentable hosts. Here, the full biosynthetic pathway of artemisinin, originating from Artemisia annua, was integrated into the moss Physcomitrella patens. Different combinations of the five artemisinin biosynthesis genes were ectopically expressed in P. patens to study biosynthesis pathway activity, but also to ensure survival of successful transformants. Transformation of the first pathway gene, ADS, into P. patens resulted in the accumulation of the expected metabolite, amorpha-4,11-diene, and also accumulation of a second product, arteannuin B. This demonstrates the presence of endogenous promiscuous enzyme activity, possibly cytochrome P450s, in P. patens. Introduction of three pathway genes, ADSCYP71AV1- ADH1 or ADS-DBR2-ALDH1 both led to the accumulation of artemisinin, hinting at the presence of one or more endogenous enzymes in P. patens that can complement the partial pathways to full pathway activity. Transgenic P. patens lines containing the different gene combinations produce artemisinin in varying amounts. The pathway gene expression in the transgenic moss lines correlates well with the chemical profile of pathway products. Moreover, expression of the pathway genes resulted in lipid body formation in all transgenic moss lines, suggesting that these may have a function in sequestration of heterologous metabolites. This work thus provides novel insights into the metabolic response of P. patens and its complementation potential for A. annua artemisinin pathway genes. Identification of the related endogenous P. patens genes could contribute to a further successful metabolic engineering of artemisinin biosynthesis, as well as bioengineering of other high-value terpenoids in P. patens.
Keywords	Artemisinin ; Biotechnology ; Malaria ; Physcomitrella patens ; Sesquiterpenoids
Subject code	570
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	1413402-0
ISSN	1431-5165 ; 1420-3049
ISSN	1431-5165 ; 1420-3049
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Increase in Vitamin D but not Regulatory T Cells following Ultraviolet B Phototherapy of Patients with Atopic Dermatitis.

Simonsen, Stine / Bonefeld, Charlotte M / Thyssen, Jacob P / Geisler, Carsten / Skov, Lone

Acta dermato-venereologica

2018 Volume 99, Issue 2, Page(s) 139–145

Abstract: ... regulatory T cells in patients with atopic dermatitis receiving narrow-band ultraviolet B (nbUVB ...

Abstract	This study investigated serum 25-hydroxyvitamin D (25(OH)D) concentrations and circulating regulatory T cells in patients with atopic dermatitis receiving narrow-band ultraviolet B (nbUVB) phototherapy. Thirty adult patients with atopic dermatitis were included. Blood samples were collected at baseline and at weeks 2 and 4 of nbUVB phototherapy. Skin biopsies were taken at baseline and at week 4. Serum 25(OH)D concentrations increased significantly following nbUVB phototherapy (estimate of change from baseline to week 2: 32.00 nmol/l, confidence interval (CI) 20.48-43.52, p < 0.0001, n = 25; and from baseline to week 4: 50.30 nmol/l, CI 37.28-63.33, p < 0.0001, n = 18). This increase was independent of the filaggrin gene FLG loss-of-function mutation status. Flow cytometry showed no significant change in regulatory T cells or cytokine profiles of T cells in blood. Real-time quantitative PCR showed no change in skin cytokine levels. In conclusion, nbUVB phototherapy was associated with increased serum 25(OH)D concentrations, but not changes in circulating regulatory T cells in patients with atopic dermatitis.
MeSH term(s)	Adult ; Biomarkers/blood ; CD4 Lymphocyte Count ; Dermatitis, Atopic/blood ; Dermatitis, Atopic/diagnosis ; Dermatitis, Atopic/immunology ; Dermatitis, Atopic/radiotherapy ; Female ; Humans ; Male ; Middle Aged ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/radiation effects ; Time Factors ; Treatment Outcome ; Ultraviolet Therapy ; Vitamin D/analogs & derivatives ; Vitamin D/blood ; Young Adult
Chemical Substances	Biomarkers ; Vitamin D (1406-16-2) ; 25-hydroxyvitamin D (A288AR3C9H)
Language	English
Publishing date	2018-09-13
Publishing country	Sweden
Document type	Journal Article
ZDB-ID	80007-7
ISSN	1651-2057 ; 0001-5555
ISSN (online)	1651-2057
ISSN	0001-5555
DOI	10.2340/00015555-3050
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Article ; Online: Expression of Filaggrin and its Degradation Products in Human Skin Following Erythemal Doses of Ultraviolet B Irradiation.

Simonsen, Stine / Thyssen, Jacob P / Heegaard, Steffen / Kezic, Sanja / Skov, Lone

Acta dermato-venereologica

2017 Volume 97, Issue 7, Page(s) 797–801

Abstract: Epidermal filaggrin level is affected by ultraviolet B irradiation in animal and ... experimental models. This study examined the effect of ultraviolet B irradiation on epidermal filaggrin and natural ... doses of ultraviolet B on the skin. Biopsies and tape strips were collected from skin irradiated 24 and ...

Abstract	Epidermal filaggrin level is affected by ultraviolet B irradiation in animal and experimental models. This study examined the effect of ultraviolet B irradiation on epidermal filaggrin and natural moisturizing factors in vivo in healthy adults (n = 22). Participants were irradiated with 2 minimal erythema doses of ultraviolet B on the skin. Biopsies and tape strips were collected from skin irradiated 24 and 72 h earlier and from non-irradiated skin (control). Real-time quantitative PCR on skin biopsies showed significantly reduced profilaggrin mRNA expression 24 h after irradiation (mean relative mRNA expression ± standard deviation: control, 3.86 ± 2.06 vs. 24 h, 1.52 ± 0.640; p = 0.02; n = 8). Immunohistochemistry showed aberrant spatial distribution of filaggrin protein 72 h after irradiation (n = 3). High-pressure liquid chromatography of tape extracts showed no change in mean total natural moisturizing factor levels after irradiation, but mean trans-urocanic acid was significantly reduced, as expected (n = 8). In conclusion, erythemal doses of ultraviolet B exert acute effects on profilaggrin mRNA and filaggrin protein in human skin in vivo.
Language	English
Publishing date	2017-07-06
Publishing country	Sweden
Document type	Journal Article
ZDB-ID	80007-7
ISSN	1651-2057 ; 0001-5555
ISSN (online)	1651-2057
ISSN	0001-5555
DOI	10.2340/00015555-2662
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Article ; Online: No difference in ultraviolet B-induced changes in antigen-presenting cells and cytokines between patients with and without loss-of-function mutations in FLG.

Simonsen, S / Bonefeld, C M / Thyssen, J P / Christiansen, A T / Geisler, C / Skov, L

The British journal of dermatology

2018 Volume 179, Issue 1, Page(s) 205–207

MeSH term(s)	Blister/etiology ; Blister/pathology ; Cell Count ; Cell Separation ; Cytokines/metabolism ; Female ; Flow Cytometry ; Genetic Predisposition to Disease ; Heterozygote ; Humans ; Intermediate Filament Proteins/genetics ; Langerhans Cells/radiation effects ; Loss of Function Mutation ; Male ; Monocytes/radiation effects ; Photosensitivity Disorders/etiology ; Photosensitivity Disorders/pathology ; Skin/metabolism ; Skin/pathology ; Skin/radiation effects ; Skin Tests/methods ; Suction/adverse effects ; Ultraviolet Rays/adverse effects
Chemical Substances	Cytokines ; Intermediate Filament Proteins ; filaggrin
Language	English
Publishing date	2018-05-05
Publishing country	England
Document type	Letter
ZDB-ID	80076-4
ISSN	1365-2133 ; 0007-0963
ISSN (online)	1365-2133
ISSN	0007-0963
DOI	10.1111/bjd.16394
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Article: Comparative and genetic studies of isozymes in resynthesized and cultivated Brassica napus L., B. campestris L. and B. alboglabra Bailey.

Chen, B Y / Heneen, W K / Simonsen, V

TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik

2013 Volume 77, Issue 5, Page(s) 673–679

Abstract: ... parental diploid species, B. campestris and B. alboglabra. Comparisons were also made with cultivated B ... within or between species. The polymorphic enzyme patterns observed in the newly resynthesized B. napus ... Analysis of the glucosephosphate isomerase enzyme in a breeding line (Sv 02372) of B. napus indicated ...

Abstract	Enzyme electrophoresis was used to compare newly resynthesized Brassica napus with its actual parental diploid species, B. campestris and B. alboglabra. Comparisons were also made with cultivated B. napus. Of the eight enzyme systems assayed, four were monomorphic (hexokinase, malate dehydrogenase, mannose phosphate isomerase and peroxidase), whereas the remaining four were polymorphic (glucosephosphate isomerase, leucine aminopeptidase, phosphoglucomutase and shikimate dehydrogenase), when comparisons were made within or between species. The polymorphic enzyme patterns observed in the newly resynthesized B. napus disclosed that the homoeologous loci contributed by the parental species were expressed in the amphiploid. Analysis of the glucosephosphate isomerase enzyme in a breeding line (Sv 02372) of B. napus indicated that, in this case, the gene originating from B. campestris was switched off whereas that of B. oleracea was expressed. Duplicated enzyme loci were observed in B. campestris and B. alboglabra, thus providing additional evidence to support the hypothesis that these species are actually secondary polyploids derived from an unknown archetype of x=6.
Language	English
Publishing date	2013-11-15
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2170-2
ISSN	1432-2242 ; 0040-5752
ISSN (online)	1432-2242
ISSN	0040-5752
DOI	10.1007/BF00261242
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