| 1. |
- Abdullah Nasir, Ahmad, et al.
(författare)
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Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Netrin-1 is a secreted protein that is well known for its involvement in axonal guidance during embryonic development and as an enhancer of cancer cell metastasis. Despite extensive efforts, the molecular mechanisms behind many of the physiological functions of netrin-1 have remained elusive. Here, we show that netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling in various cellular systems, including a mutually inhibitory interaction with the BMP-promoting function of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins. The BMP inhibitory function of netrin-1 in mouse embryonic fibroblasts was dependent on the netrin receptor neogenin, with the expression level regulated by both netrin-1 and LRIG proteins. Our results reveal a previously unrecognized function of netrin-1 that may help to explain several of the developmental, physiological, and cancer-promoting functions of netrins at the signal transduction level.
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| 2. |
- Abzhandadze, Tamar, 1980, et al.
(författare)
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Transforming self-reported outcomes from a stroke register to the modified Rankin Scale: a cross-sectional, explorative study
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to create an algorithm to transform self-reported outcomes from a stroke register to the modified Rankin Scale (mRS). Two stroke registers were used: the Vaststroke, a local register in Gothenburg, Sweden, and the Riksstroke, a Swedish national register. The reference variable, mRS (from Vaststroke), was mapped with seven self-reported questions from Riksstroke. The transformation algorithm was created as a result of manual mapping performed by healthcare professionals. A supervised machine learning method-decision tree-was used to further evaluate the transformation algorithm. Of 1145 patients, 54% were male, the mean age was 71 y. The mRS grades 0, 1 and 2 could not be distinguished as a result of manual mapping or by using the decision tree analysis. Thus, these grades were merged. With manual mapping, 78% of the patients were correctly classified, and the level of agreement was almost perfect, weighted Kappa (K-w) was 0.81. With the decision tree, 80% of the patients were correctly classified, and substantial agreement was achieved, K-w=0.67. The self-reported outcomes from a stroke register can be transformed to the mRS. A mRS algorithm based on manual mapping might be useful for researchers using self-reported questionnaire data.
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| 3. |
- Ahlinder, Jon, et al.
(författare)
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Life stage-specific inbreeding depression in long-lived Pinaceae species depends on population connectivity
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Inbreeding depression (ID) is a fundamental selective pressure that shapes mating systems and population genetic structures in plants. Although it has been shown that ID varies over the life stages of shorter-lived plants, less is known about how the fitness effects of inbreeding vary across life stages in long-lived species. We conducted a literature survey in the Pinaceae, a tree family known to harbour some of the highest mutational loads ever reported. Using a meta-regression model, we investigated distributions of inbreeding depression over life stages, adjusting for effects of inbreeding levels and the genetic differentiation of populations within species. The final dataset contained 147 estimates of ID across life stages from 41 studies. 44 Fst estimates were collected from 40 peer-reviewed studies for the 18 species to aid genetic differentiation modelling. Partitioning species into fragmented and well-connected groups using Fst resulted in the best way (i.e. trade-off between high goodness-of-fit of the model to the data and reduced model complexity) to incorporate genetic connectivity in the meta-regression analysis. Inclusion of a life stage term and its interaction with the inbreeding coefficient (F) dramatically increased model precision. We observed that the correlation between ID and F was significant at the earliest life stage. Although partitioning of species populations into fragmented and well-connected groups explained little of the between-study heterogeneity, the inclusion of an interaction between life stage and population differentiation revealed that populations with fragmented distributions suffered lower inbreeding depression at early embryonic stages than species with well-connected populations. There was no evidence for increased ID in late life stages in well-connected populations, although ID tended to increase across life stages in the fragmented group. These findings suggest that life stage data should be included in inbreeding depression studies and that inbreeding needs to be managed over life stages in commercial populations of long-lived plants.
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| 4. |
- Ahlqvist, Viktor H., et al.
(författare)
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Birth weight and grip strength in young Swedish males : a longitudinal matched sibling analysis and across all body mass index ranges
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Low birth weight is associated with a lower grip strength later in life. However, associations between birth weight among infants born at-term and factors driving associations between birth weight and grip strength are largely unknown. A cohort of 144,369 young men born at-term, including 10,791 individuals who had at least one male sibling/s, were followed until conscription where they performed a grip strength test. We used linear and non-linear regression analyses in the full cohort, and fixed-effects regression analyses in the sibling cohort, to address confounding by factors that are shared between siblings. After adjustment, each unit increase in birth weight z-score was associated with increases of 17.7 (95% CI, 17.2-18.2) and 13.4 (10.1-16.6) newton grip strength, which converts to approximately 1.8 and 1.4 kilogram-force in the full and within-families cohorts, respectively. The associations did not vary with young adulthood BMI. Birth weight, within the at-term range, is robustly positively associated with grip strength in young adulthood among men across all BMI categories and associations appears to be mainly driven by factors that are not shared between siblings. These findings underline the importance of recognizing the influence of low birth weight, also within the at-termrange, on young adulthood muscle strength.
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| 5. |
- Ahmad, Irfan, et al.
(författare)
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A Cyclic-di-GMP signalling network regulates biofilm formation and surface associated motility of Acinetobacter baumannii 17978
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Acinetobacter baumannii has emerged as an increasing multidrug-resistant threat in hospitals and a common opportunistic nosocomial pathogen worldwide. However, molecular details of the pathogenesis and physiology of this bacterium largely remain to be elucidated. Here we identify and characterize the c-di-GMP signalling network and assess its role in biofilm formation and surface associated motility. Bioinformatic analysis revealed eleven candidate genes for c-di-GMP metabolizing proteins (GGDEF/EAL domain proteins) in the genome of A. baumannii strain 17978. Enzymatic activity of the encoded proteins was assessed by molecular cloning and expression in the model organisms Salmonella typhimurium and Vibrio cholerae. Ten of the eleven GGDEF/EAL proteins altered the rdar morphotype of S. typhimurium and the rugose morphotype of V. cholerae. The over expression of three GGDEF proteins exerted a pronounced effect on colony formation of A. baumannii on Congo Red agar plates. Distinct panels of GGDEF/EAL proteins were found to alter biofilm formation and surface associated motility of A. baumannii upon over expression. The GGDEF protein A1S_3296 appeared as a major diguanylate cyclase regulating macro-colony formation, biofilm formation and the surface associated motility. AIS_3296 promotes Csu pili mediated biofilm formation. We conclude that a functional c-di-GMP signalling network in A. baumannii regulates biofilm formation and surface associated motility of this increasingly important opportunistic bacterial pathogen.
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| 6. |
- Akkaya, Munir, et al.
(författare)
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Testing the impact of a single nucleotide polymorphism in a Plasmodium berghei ApiAP2 transcription factor on experimental cerebral malaria in mice
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral malaria (CM) is the deadliest form of severe Plasmodium infections. Currently, we have limited understanding of the mechanisms by which Plasmodium parasites induce CM. The mouse model of CM, experimental CM (ECM), induced by infection with the rodent parasite, Plasmodium berghei ANKA (PbANKA) has been extensively used to study the pathophysiology of CM. Recent genomic analyses revealed that the coding regions of PbANKA and the closely related Plasmodium berghei NK65 (PbNK65), that does not cause ECM, differ in only 21 single nucleotide polymorphysims (SNPs). Thus, the SNP-containing genes might contribute to the pathogenesis of ECM. Although the majority of these SNPs are located in genes of unknown function, one SNP is located in the DNA binding site of a member of the Plasmodium ApiAP2 transcription factor family, that we recently showed functions as a virulence factor alternating the host's immune response to the parasite. Here, we investigated the impact of this SNP on the development of ECM. Our results using CRISPR-Cas9 engineered parasites indicate that despite its immune modulatory function, the SNP is neither necessary nor sufficient to induce ECM and thus cannot account for parasite strain-specific differences in ECM phenotypes.
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| 7. |
- Alakpa, Enateri V., et al.
(författare)
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Improving cartilage phenotype from differentiated pericytes in tunable peptide hydrogels
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Differentiation of stem cells to chondrocytes in vitro usually results in a heterogeneous phenotype. This is evident in the often detected over expression of type X collagen which, in hyaline cartilage structure is not characteristic of the mid-zone but of the deep-zone ossifying tissue. Methods to better match cartilage developed in vitro to characteristic in vivo features are therefore highly desirable in regenerative medicine. This study compares phenotype characteristics between pericytes, obtained from human adipose tissue, differentiated using diphenylalanine/serine (F2/S) peptide hydrogels with the more widely used chemical induced method for chondrogenesis. Significantly higher levels of type II collagen were noted when pericytes undergo chondrogenesis in the hydrogel in the absence of induction media. There is also a balanced expression of collagen relative to aggrecan production, a feature which was biased toward collagen production when cells were cultured with induction media. Lastly, metabolic profiles of each system show considerable overlap between both differentiation methods but subtle differences which potentially give rise to their resultant phenotype can be ascertained. The study highlights how material and chemical alterations in the cellular microenvironment have wide ranging effects on resultant tissue type.
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| 8. |
- Alam, Athar, et al.
(författare)
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ClpB mutants of Francisella tularensis subspecies holarctica and tularensis are defective for type VI secretion and intracellular replication
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Francisella tularensis, a highly infectious, intracellular bacterium possesses an atypical type VI secretion system (T6SS), which is essential for the virulence of the bacterium. Recent data suggest that the HSP100 family member, ClpB, is involved in T6SS disassembly in the subspecies Francisella novicida. Here, we investigated the role of ClpB for the function of the T6SS and for phenotypic characteristics of the human pathogenic subspecies holarctica and tularensis. The Delta clpB mutants of the human live vaccine strain, LVS, belonging to subspecies holarctica, and the highly virulent SCHU S4 strain, belonging to subspecies tularensis, both showed extreme susceptibility to heat shock and low pH, severely impaired type VI secretion (T6S), and significant, but impaired intracellular replication compared to the wild-type strains. Moreover, they showed essentially intact phagosomal escape. Infection of mice demonstrated that both Delta clpB mutants were highly attenuated, but the SCHU S4 mutant showed more effective replication than the LVS strain. Collectively, our data demonstrate that ClpB performs multiple functions in the F. tularensis subspecies holarctica and tularensis and its function is important for T6S, intracellular replication, and virulence.
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| 9. |
- Alaridah, Nader, et al.
(författare)
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Transmission dynamics study of tuberculosis isolates with whole genome sequencing in southern Sweden
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological contact tracing complemented with genotyping of clinical Mycobacterium tuberculosis isolates is important for understanding disease transmission. In Sweden, tuberculosis (TB) is mostly reported in migrant and homeless where epidemiologic contact tracing could pose a problem. This study compared epidemiologic linking with genotyping in a low burden country. Mycobacterium tuberculosis isolates (n = 93) collected at Scania University Hospital in Southern Sweden were analysed with the standard genotyping method mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) and the results were compared with whole genome sequencing (WGS). Using a maximum of twelve single nucleotide polymorphisms (SNPs) as the upper threshold of genomic relatedness noted among hosts, we identified 18 clusters with WGS comprising 52 patients with overall pairwise genetic maximum distances ranging from zero to nine SNPs. MIRU-VNTR and WGS clustered the same isolates, although the distribution differed depending on MIRU-VNTR limitations. Both genotyping techniques identified clusters where epidemiologic linking was insufficient, although WGS had higher correlation with epidemiologic data. To summarize, WGS provided better resolution of transmission than MIRU-VNTR in a setting with low TB incidence. WGS predicted epidemiologic links better which could consolidate and correct the epidemiologically linked cases, avoiding thus false clustering.
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| 10. |
- Alegria Zufia, Javier, Ph.D. 1992-, et al.
(författare)
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Seasonal dynamics in picocyanobacterial abundance and clade composition at coastal and offshore stations in the Baltic Sea
- 2022
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Ingår i: Scientific Reports. - London : Nature Publishing Group. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Picocyanobacteria (< 2 um in diameter) are significant contributors to total phytoplankton biomass. Due to the high diversity within this group, their seasonal dynamics and relationship with environmental parameters, especially in brackish waters, are largely unknown. In this study, the abundance and community composition of phycoerythrin rich picocyanobacteria (PE-SYN) and phycocyanin rich picocyanobacteria (PC-SYN) were monitored at a coastal (K-station) and at an offshore station (LMO; similar to 10 km from land) in the Baltic Sea over three years (2018-2020). Cell abundances of picocyanobacteria correlated positively to temperature and negatively to nitrate (NO3) concentration. While PE-SYN abundance correlated to the presence of nitrogen fixers, PC-SYN abundance was linked to stratification/shallow waters. The picocyanobacterial targeted amplicon sequencing revealed an unprecedented diversity of 2169 picocyanobacterial amplicons sequence variants (ASVs). A unique assemblage of distinct picocyanobacterial clades across seasons was identified. Clade A/B dominated the picocyanobacterial community, except during summer when low NO3, high phosphate (PO4) concentrations and warm temperatures promoted S5.2 dominance. This study, providing multiyear data, links picocyanobacterial populations to environmental parameters. The difference in the response of the two functional groups and clades underscore the need for further high-resolution studies to understand their role in the ecosystem.
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