Publications by authors named "Lars Paulin"

167 Publications

Improved chromosome-level genome assembly of the Glanville fritillary butterfly (Melitaea cinxia) integrating Pacific Biosciences long reads and a high-density linkage map.

Gigascience 2022 Jan;11(1)

Institute of Biotechnology, University of Helsinki, 00790 Helsinki, Finland.

Background: The Glanville fritillary (Melitaea cinxia) butterfly is a model system for metapopulation dynamics research in fragmented landscapes. Here, we provide a chromosome-level assembly of the butterfly's genome produced from Pacific Biosciences sequencing of a pool of males, combined with a linkage map from population crosses.

Results: The final assembly size of 484 Mb is an increase of 94 Mb on the previously published genome. Estimation of the completeness of the genome with BUSCO indicates that the genome contains 92-94% of the BUSCO genes in complete and single copies. We predicted 14,810 genes using the MAKER pipeline and manually curated 1,232 of these gene models.

Conclusions: The genome and its annotated gene models are a valuable resource for future comparative genomics, molecular biology, transcriptome, and genetics studies on this species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gigascience/giab097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8756199PMC
January 2022

Alu element in the RNA binding motif protein, X-linked 2 (RBMX2) gene found to be linked to bipolar disorder.

PLoS One 2021 16;16(12):e0261170. Epub 2021 Dec 16.

Pacific Biosciences, Menlo Park, CA, United States of America.

Objective: We have used long-read single molecule, real-time (SMRT) sequencing to fully characterize a ~12Mb genomic region on chromosome Xq24-q27, significantly linked to bipolar disorder (BD) in an extended family from a genetic sub-isolate. This family segregates BD in at least four generations with 24 affected individuals.

Methods: We selected 16 family members for targeted sequencing. The selected individuals either carried the disease haplotype, were non-carriers of the disease haplotype, or served as married-in controls. We designed hybrid capture probes enriching for 5-9Kb fragments spanning the entire 12Mb region that were then sequenced to screen for candidate structural variants (SVs) that could explain the increased risk for BD in this extended family.

Results: Altogether, 201 variants were detected in the critically linked region. Although most of these represented common variants, three variants emerged that showed near-perfect segregation among all BD type I affected individuals. Two of the SVs were identified in or near genes belonging to the RNA Binding Motif Protein, X-Linked (RBMX) gene family-a 330bp Alu (subfamily AluYa5) deletion in intron 3 of the RBMX2 gene and an intergenic 27bp tandem repeat deletion between the RBMX and G protein-coupled receptor 101 (GPR101) genes. The third SV was a 50bp tandem repeat insertion in intron 1 of the Coagulation Factor IX (F9) gene.

Conclusions: Among the three genetically linked SVs, additional evidence supported the Alu element deletion in RBMX2 as the leading candidate for contributing directly to the disease development of BD type I in this extended family.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261170PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675739PMC
January 2022

Genomic convergence between Akkermansia muciniphila in different mammalian hosts.

BMC Microbiol 2021 10 29;21(1):298. Epub 2021 Oct 29.

Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.

Background: Akkermansia muciniphila is a member of the human gut microbiota where it resides in the mucus layer and uses mucin as the sole carbon, nitrogen and energy source. A. muciniphila is the only representative of the Verrucomicrobia phylum in the human gut. However, A. muciniphila 16S rRNA gene sequences have also been found in the intestines of many vertebrates.

Results: We detected A. muciniphila-like bacteria in the intestines of animals belonging to 15 out of 16 mammalian orders. In addition, other species belonging to the Verrucomicrobia phylum were detected in fecal samples. We isolated 10 new A. muciniphila strains from the feces of chimpanzee, siamang, mouse, pig, reindeer, horse and elephant. The physiology and genome of these strains were highly similar in comparison to the type strain A. muciniphila Muc. Overall, the genomes of the new strains showed high average nucleotide identity (93.9 to 99.7%). In these genomes, we detected considerable conservation of at least 75 of the 78 mucin degradation genes that were previously detected in the genome of the type strain Muc.

Conclusions: The low genomic divergence observed in the new strains may indicate that A. muciniphila favors mucosal colonization independent of the differences in hosts. In addition, the conserved mucus degradation capability points towards a similar beneficial role of the new strains in regulating host metabolic health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12866-021-02360-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555344PMC
October 2021

SARS-CoV-2 variant with mutations in N gene affecting detection by widely used PCR primers.

J Med Virol 2021 Oct 26. Epub 2021 Oct 26.

Vita Laboratory, Helsinki, Finland.

While most of the spontaneous mutations in the viral genome have no functional, diagnostic, or clinical consequences, some have. In February 2021, we noticed in Southern Finland coronavirus disease 2019 cases where two commercial polymerase chain reaction (PCR) analyses failed to recognize the used N gene target but recognized the other target gene of severe acute respiratory syndrome coronavirus 2. Complete viral genome sequence analysis of the strains revealed several mutations that were not found at that time in public databases. A short 3 bp deletion and three subsequent single nucleotide polymorphisms in the N gene were found exactly at the site where an early published and widely used N gene-based PCR primer is located, explaining the negative results in the N gene PCR. Later the variant strain was identified as a member of the B.1.1.318 Pango lineage that had first been found from Nigerian samples collected in January 2021. This strain shares with the Beta variant the S gene E484K mutation linked to impaired vaccine protection, but differs from this variant in several other ways, for example by deletions in the N gene region. Mutations in the N gene causing diagnostic resistance and on the other hand E484K mutation in the causing altered infectivity warrants careful inspection on virus variants that might get underdiagnosed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmv.27418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8661661PMC
October 2021

Comparative Genomics of 42 Strains.

Antibiotics (Basel) 2021 Jun 18;10(6). Epub 2021 Jun 18.

Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Mustialankatu 1, 00790 Helsinki, Finland.

For the last 13 years, the fur industry in Europe has suffered from epidemic spouts of a severe necrotizing pyoderma. It affects all species currently farmed for fur and causes animal welfare problems and significant losses to the farmers. The causative agent of this disease was identified as . Previously, this bacterium has been isolated from seals and other marine mammals, apparently causing wound and lung infections. Attempts at antibiotic treatment have been unsuccessful and the current advice on preventing the disease is to cull all animals with clinical signs. This poses an urgent question regarding possible vaccine development, as well as the need for further understanding of the pathogenicity of this organism. This study compared the whole genomes of 42 strains isolated from seals, blue foxes, finnraccoons, mink and otter. The sequences were created using the Illumina technology and annotations were done using the RAST pipeline. A phylogenetic analysis identified a clear separation between the seal strains and the fur-animal-derived isolates, but also indicated that the bacterium readily adapts to new environments and host species with reasonable diversity. A pan- and core-genome was created and analyzed for proteins. A further analysis identified several virulence factors as well as multiple putative and secreted proteins of special interest for vaccine development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antibiotics10060740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235330PMC
June 2021

Gut Microbiome Signatures of Risk and Prodromal Markers of Parkinson Disease.

Ann Neurol 2021 09 16;90(3):E1-E12. Epub 2021 Jul 16.

Department of Neurology, Helsinki University Hospital and Department of Clinical Neurosciences (Neurology), University of Helsinki, Helsinki, Finland.

Objective: Alterations of the gut microbiome in Parkinson disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they relate to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition.

Methods: Established risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function, and medication were studied in relation to bacterial α-/β-diversity, enterotypes, and differential abundance in stool samples of 666 elderly TREND (Tübingen Evaluation of Risk Factors for Early Detection of Neurodegeneration) study participants.

Results: Among risk and prodromal markers, physical inactivity, occupational solvent exposure, and constipation showed associations with α-diversity. Physical inactivity, sex, constipation, possible rapid eye movement sleep behavior disorder (RBD), and smoking were associated with β-diversity. Subthreshold parkinsonism and physical inactivity showed an interaction effect. Among other factors, age and urate-lowering medication were associated with α- and β-diversity. Constipation was highest in individuals with the Firmicutes-enriched enterotype, and physical inactivity was most frequent in the Bacteroides-enriched enterotype. Constipation was lowest and subthreshold parkinsonism least frequent in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical inactivity, possible RBD, smoking, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history, and the prodromal PD probability showed no significant microbiome associations.

Interpretation: Several risk and prodromal markers of PD are associated with gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases. ANN NEUROL 2021;90:E1-E12.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.26128DOI Listing
September 2021

The complete genome sequence of Listeria monocytogenes strain S2542 and expression of selected genes under high-pressure processing.

BMC Res Notes 2021 Apr 15;14(1):137. Epub 2021 Apr 15.

Institute of Biotechnology, University of Helsinki, Helsinki, Finland.

Objectives: The study aims to generate the whole genome sequence of L. monocytogenes strain S2542 and to compare it to the genomes of strains RO15 and ScottA. In addition, we aimed to compare gene expression profiles of L. monocytogenes strains S2542, ScottA and RO15 after high-pressure processing (HPP) using ddPCR.

Results: The whole genome sequence of L. monocytogenes S2542 indicates that this strain belongs to serotype 4b, in contrast to the previously reported serotype 1/2a. Strain S2542 appears to be more susceptible to the treatment at 400 MPa compared to RO15 and ScottA strains. In contrast to RO15 and ScottA strains, viable cell counts of strain S2542 were below the limit of detection after HPP (400 MPa/8 min) when stored at 8 °C for 24 and 48 h. The transcriptional response of all three strains to HPP was not significantly different.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13104-021-05555-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048338PMC
April 2021

A transcriptomic view to wounding response in young Scots pine stems.

Sci Rep 2021 02 12;11(1):3778. Epub 2021 Feb 12.

Department of Agricultural Sciences, Viikki Plant Science Centre, University of Helsinki, P.O. Box 27, 00014, Helsinki, Finland.

We studied the stress response of five-year-old Scots pine xylem to mechanical wounding using RNA sequencing. In general, we observed a bimodal response in pine xylem after wounding. Transcripts associated with water deficit stress, defence, and cell wall modification were induced at the earliest time point of three hours; at the same time, growth-related processes were down-regulated. A second temporal wave was triggered either at the middle and/or at the late time points (one and four days). Secondary metabolism, such as stilbene and lignan biosynthesis started one day after wounding. Scots pine synthesises the stilbenes pinosylvin and its monomethyl ether both as constitutive and induced defence compounds. Stilbene biosynthesis is induced by wounding, pathogens and UV stress, but is also developmentally regulated when heartwood is formed. Comparison of wounding responses to heartwood formation shows that many induced processes (in addition to stilbene biosynthesis) are similar and relate to defence or desiccation stress, but often specific transcripts are up-regulated in the developmental and wounding induced contexts. Pine resin biosynthesis was not induced in response to wounding, at least not during the first four days.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-82848-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881122PMC
February 2021

High-pressure processing-induced transcriptome response during recovery of Listeria monocytogenes.

BMC Genomics 2021 Feb 12;22(1):117. Epub 2021 Feb 12.

Institute of Biotechnology, University of Helsinki, Helsinki, Finland.

Background: High-pressure processing (HPP) is a commonly used technique in the food industry to inactivate pathogens, including L. monocytogenes. It has been shown that L. monocytogenes is able to recover from HPP injuries and can start to grow again during long-term cold storage. To date, the gene expression profiling of L. monocytogenes during HPP damage recovery at cooling temperature has not been studied. In order identify key genes that play a role in recovery of the damage caused by HPP treatment, we performed RNA-sequencing (RNA-seq) for two L. monocytogenes strains (barotolerant RO15 and barosensitive ScottA) at nine selected time points (up to 48 h) after treatment with two pressure levels (200 and 400 MPa).

Results: The results showed that a general stress response was activated by SigB after HPP treatment. In addition, the phosphotransferase system (PTS; mostly fructose-, mannose-, galactitol-, cellobiose-, and ascorbate-specific PTS systems), protein folding, and cobalamin biosynthesis were the most upregulated genes during HPP damage recovery. We observed that cell-division-related genes (divIC, dicIVA, ftsE, and ftsX) were downregulated. By contrast, peptidoglycan-synthesis genes (murG, murC, and pbp2A) were upregulated. This indicates that cell-wall repair occurs as a part of HPP damage recovery. We also observed that prophage genes, including anti-CRISPR genes, were induced by HPP. Interestingly, a large amount of RNA-seq data (up to 85%) was mapped to Rli47, which is a non-coding RNA that is upregulated after HPP. Thus, we predicted that Rli47 plays a role in HPP damage recovery in L. monocytogenes. Moreover, gene-deletion experiments showed that amongst peptidoglycan biosynthesis genes, pbp2A mutants are more sensitive to HPP.

Conclusions: We identified several genes and mechanisms that may play a role in recovery from HPP damage of L. monocytogenes. Our study contributes to new information on pathogen inactivation by HPP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-021-07407-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881616PMC
February 2021

Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson's disease.

Mol Neurodegener 2021 02 8;16(1). Epub 2021 Feb 8.

Department of Neurology, Helsinki University Hospital, and Department of Neurological Sciences (Neurology), University of Helsinki, ward K4A, Haartmaninkatu 4, FI-00290, Helsinki, Finland.

Background: Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson's disease (PD), but how these factors are linked and how they contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD.

Methods: Stool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota.

Results: Calprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of SCFAs, inflammatory factors, and zonulin in stool. Certain relationships differed between patients and controls and by sex.

Conclusions: Intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are distinct in PD and are sex-dependent. This study revealed potential alterations in microbiota-host interactions and links between earlier PD onset and intestinal inflammatory responses and reduced SCFA levels, highlighting candidate molecules and pathways which may contribute to PD pathogenesis and clinical presentation and which warrant further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13024-021-00427-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869249PMC
February 2021

Subgingival microbiota in a population with and without cognitive dysfunction.

J Oral Microbiol 2021 Jan 15;13(1):1854552. Epub 2021 Jan 15.

Unit of Periodontology, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.

: The aim of this study was to compare the subgingival microbiota of people with Alzheimer´s disease (AD), mild cognitive impairment (MCI), subjective cognitive decline (SCD) and cognitively healthy individuals. : The study population was recruited from 2013 to 2017 and comprised 132 cases recently diagnosed with AD (n = 46), MCI (n = 40) or SCD (n = 46), and 63 cognitively healthy controls. Subgingival samples were collected, and the microbiotas were characterized by gene sequencing. : The relative abundance of the ten most common genera did not differ between the cases and control groups. However, the microbial richness and evenness were higher in cases than in controls and differed across the four groups. The variables with the greatest influence on the microbial community composition were related to periodontal disease followed by body mass index, study group affiliation and smoking. Ten taxa exhibited significant differences between case participants and controls. Two Operational Taxonomic Units were particularly abundant in AD compared to controls: , which was also associated with deep periodontal pockets, and a [G-7] bacterium. : It is concluded that in individuals with cognitive impairment or AD, the subgingival microbiota exhibits shifts typical of periodontal disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/20002297.2020.1854552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833025PMC
January 2021

Life-history genomic regions explain differences in Atlantic salmon marine diet specialization.

J Anim Ecol 2020 11 28;89(11):2677-2691. Epub 2020 Sep 28.

Organismal and Evolutionary Biology Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.

Animals employ various foraging strategies along their ontogeny to acquire energy, and with varying degree of efficiencies, to support growth, maturation and subsequent reproduction events. Individuals that can efficiently acquire energy early are more likely to mature at an earlier age, as a result of faster energy gain which can fuel maturation and reproduction. We aimed to test the hypothesis that heritable resource acquisition variation that covaries with efficiency along the ontogeny would influence maturation timing of individuals. To test this hypothesis, we utilized Atlantic salmon as a model which exhibits a simple, hence trackable, genetic control of maturation age. We then monitored the variation in diet acquisition (quantified as stomach fullness and composition) of individuals with different ages, and linked it with genomic regions (haploblocks) that were previously identified to be associated with age-at-maturity. Consistent with the hypothesis, we demonstrated that one of the life-history genomic regions tested (six6) was indeed associated with age-dependent differences in stomach fullness. Prey composition was marginally linked to six6, and suggestively (but non-significantly) to vgll3 genomic regions. We further showed Atlantic salmon switched to the so-called 'feast and famine' strategy along the ontogeny, where older age groups exhibited heavier stomach content, but that came at the expense of running on empty more often. These results suggest genetic variation underlying resource utilization may explain the genetic basis of age structure in Atlantic salmon. Given that ontogenetic diet has a genetic component and the strong spatial diversity associated with these genomic regions, we predict populations with diverse maturation age will have diverse evolutionary responses to future changes in marine food web structures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1365-2656.13324DOI Listing
November 2020

Transcriptomic time-series analysis of cold- and heat-shock response in psychrotrophic lactic acid bacteria.

BMC Genomics 2021 Jan 7;22(1):28. Epub 2021 Jan 7.

Institute of Biotechnology, University of Helsinki, Helsinki, Finland.

Background: Psychrotrophic lactic acid bacteria (LAB) species are the dominant species in the microbiota of cold-stored modified-atmosphere-packaged food products and are the main cause of food spoilage. Despite the importance of psychrotrophic LAB, their response to cold or heat has not been studied. Here, we studied the transcriptome-level cold- and heat-shock response of spoilage lactic acid bacteria with time-series RNA-seq for Le. gelidum, Lc. piscium, and P. oligofermentans at 0 °C, 4 °C, 14 °C, 25 °C, and 28 °C.

Results: We observed that the cold-shock protein A (cspA) gene was the main cold-shock protein gene in all three species. Our results indicated that DEAD-box RNA helicase genes (cshA, cshB) also play a critical role in cold-shock response in psychrotrophic LAB. In addition, several RNase genes were involved in cold-shock response in Lc. piscium and P. oligofermentans. Moreover, gene network inference analysis provided candidate genes involved in cold-shock response. Ribosomal proteins, tRNA modification, rRNA modification, and ABC and efflux MFS transporter genes clustered with cold-shock response genes in all three species, indicating that these genes could be part of the cold-shock response machinery. Heat-shock treatment caused upregulation of Clp protease and chaperone genes in all three species. We identified transcription binding site motifs for heat-shock response genes in Le. gelidum and Lc. piscium. Finally, we showed that food spoilage-related genes were upregulated at cold temperatures.

Conclusions: The results of this study provide new insights on the cold- and heat-shock response of psychrotrophic LAB. In addition, candidate genes involved in cold- and heat-shock response predicted using gene network inference analysis could be used as targets for future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-020-07338-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788899PMC
January 2021

Gut microbiota composition is associated with narcolepsy type 1.

Neurol Neuroimmunol Neuroinflamm 2020 11 9;7(6). Epub 2020 Oct 9.

From the Institute of Biotechnology (A.L., P.P., L.P., P.A.), University of Helsinki, Finland; Sleep-Wake Disorders Unit (L.B., Y.D.), Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, University of Montpellier; National Reference Network for Narcolepsy (L.B., Y.D.), CHU Montpellier; PSNREC (L.B., Y.D.), University of Montpellier, INSERM, France; and Department of Neurology (P.P., F.S.), Helsinki University Hospital and Department of Clinical Neurosciences (Neurology), University of Helsinki, Finland.

Objective: To test the hypothesis that narcolepsy type 1 (NT1) is related to the gut microbiota, we compared the microbiota bacterial communities of patients with NT1 and control subjects.

Methods: Thirty-five patients with NT1 (51.43% women, mean age 38.29 ± 19.98 years) and 41 controls (57.14% women, mean age 36.14 ± 12.68 years) were included. Stool samples were collected, and the fecal microbiota bacterial communities were compared between patients and controls using the well-standardized 16S rRNA gene amplicon sequencing approach. We studied alpha and beta diversity and differential abundance analysis between patients and controls, and between subgroups of patients with NT1.

Results: We found no between-group differences for alpha diversity, but we discovered in NT1 a link with NT1 disease duration. We highlighted differences in the global bacterial community structure as assessed by beta diversity metrics even after adjustments for potential confounders as body mass index (BMI), often increased in NT1. Our results revealed differential abundance of several operational taxonomic units within Bacteroidetes, , and between patients and controls, but not after adjusting for BMI.

Conclusion: We provide evidence of gut microbial community structure alterations in NT1. However, further larger and longitudinal multiomics studies are required to replicate and elucidate the relationship between the gut microbiota, immunity dysregulation and NT1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/NXI.0000000000000896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577550PMC
November 2020

Immune-microbiota interaction in Finnish and Russian Karelia young people with high and low allergy prevalence.

Clin Exp Allergy 2020 10 18;50(10):1148-1158. Epub 2020 Sep 18.

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Background: After the Second World War, the population living in the Karelian region was strictly divided by the "iron curtain" between Finland and Russia. This resulted in different lifestyle, standard of living, and exposure to the environment. Allergic manifestations and sensitization to common allergens have been much more common on the Finnish compared to the Russian side.

Objective: The remarkable allergy disparity in the Finnish and Russian Karelia calls for immunological explanations.

Methods: Young people, aged 15-20 years, in the Finnish (n = 69) and Russian (n = 75) Karelia were studied. The impact of genetic variation on the phenotype was studied by a genome-wide association analysis. Differences in gene expression (transcriptome) were explored from the blood mononuclear cells (PBMC) and related to skin and nasal epithelium microbiota and sensitization.

Results: The genotype differences between the Finnish and Russian populations did not explain the allergy gap. The network of gene expression and skin and nasal microbiota was richer and more diverse in the Russian subjects. When the function of 261 differentially expressed genes was explored, innate immunity pathways were suppressed among Russians compared to Finns. Differences in the gene expression paralleled the microbiota disparity. High Acinetobacter abundance in Russians correlated with suppression of innate immune response. High-total IgE was associated with enhanced anti-viral response in the Finnish but not in the Russian subjects.

Conclusions And Clinical Relevance: Young populations living in the Finnish and Russian Karelia show marked differences in genome-wide gene expression and host contrasting skin and nasal epithelium microbiota. The rich gene-microbe network in Russians seems to result in a better-balanced innate immunity and associates with low allergy prevalence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cea.13728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589450PMC
October 2020

Survey of microbes in industrial-scale second-generation bioethanol production for better process knowledge and operation.

Appl Microbiol Biotechnol 2020 Sep 12;104(18):8049-8064. Epub 2020 Aug 12.

St1 Oy, Helsinki, Finland.

The microbes present in bioethanol production processes have been previously studied in laboratory-scale experiments, but there is a lack of information on full-scale industrial processes. In this study, the microbial communities of three industrial bioethanol production processes were characterized using several methods. The samples originated from second-generation bioethanol plants that produce fuel ethanol from biowaste, food industry side streams, or sawdust. Amplicon sequencing targeting bacteria, archaea, and fungi was used to explore the microbes present in biofuel production and anaerobic digestion of wastewater and sludge. Biofilm-forming lactic acid bacteria and wild yeasts were identified in fermentation samples of a full-scale plant that uses biowaste as feedstock. During the 20-month monitoring period, the anaerobic digester adapted to the bioethanol process waste with a shift in methanogen profile indicating acclimatization to high concentrations of ammonia. Amplicon sequencing does not specifically target living microbes. The same is true for indirect parameters, such as low pH, metabolites, or genes of lactic acid bacteria. Since rapid identification of living microbes would be indispensable for process management, a commercial method was tested that detects them by measuring the rRNA of selected microbial groups. Small-scale testing indicated that the method gives results comparable with plate counts and microscopic counting, especially for bacterial quantification. The applicability of the method was verified in an industrial bioethanol plant, inspecting the clean-in-place process quality and detecting viability during yeast separation. The results supported it as a fast and promising tool for monitoring microbes throughout industrial bioethanol processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00253-020-10818-2DOI Listing
September 2020

Complete Genome Sequences and Methylome Analyses of Cutibacterium acnes subsp. Strains DSM 16379 and DSM 1897.

Microbiol Resour Announc 2020 Jul 16;9(29). Epub 2020 Jul 16.

Department of Food and Nutrition, University of Helsinki, Helsinki, Finland

is a member of the normal human skin microbiome. However, it is also associated with skin disorders and persistent infections of orthopedic implants. Here, we announce complete genome sequences and methylomes of the subsp. strains DSM 1897 and DSM 16379 together with their active restriction-modification systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/MRA.00705-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365801PMC
July 2020

Identification and Characterization of Splicing Defects by Single-Molecule Real-Time Sequencing Technology (PacBio).

J Neuromuscul Dis 2020 ;7(4):477-481

Folkhälsan Research Center, Helsinki, Finland.

Although DNA-sequencing is the most effective procedure to achieve a molecular diagnosis in genetic diseases, complementary RNA analyses are often required.Reverse-Transcription polymerase chain reaction (RT-PCR) is still a valuable option when the clinical phenotype and/or available DNA-test results address the diagnosis toward a gene of interest or when the splicing effect of a single variant needs to be assessed.We use Single-Molecule Real-Time sequencing to detect and characterize splicing defects and single nucleotide variants in well-known disease genes (DMD, NF1, TTN). After proper optimization, the procedure could be used in the diagnostic setting, simplifying the workflow of cDNA analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JND-200523DOI Listing
July 2021

Gut Microbiome Signatures of Risk and Prodromal Markers of Parkinson Disease.

Ann Neurol 2020 08 15;88(2):320-331. Epub 2020 Jun 15.

Department of Neurology, Helsinki University Hospital and Department of Clinical Neurosciences (Neurology), University of Helsinki, Helsinki, Finland.

Objective: Alterations of the gut microbiome in Parkinson disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they relate to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition.

Methods: Established risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function, and medication were studied in relation to bacterial α-/β-diversity, enterotypes, and differential abundance in stool samples of 666 elderly TREND (Tübingen Evaluation of Risk Factors for Early Detection of Neurodegeneration) study participants.

Results: Among risk and prodromal markers, physical activity, occupational solvent exposure, and constipation showed associations with α-diversity. Physical activity, sex, constipation, possible rapid eye movement sleep behavior disorder (RBD), and smoking were associated with β-diversity. Subthreshold parkinsonism and physical activity showed an interaction effect. Among other factors, age and urate-lowering medication were associated with α- and β-diversity. Physical inactivity and constipation were highest in individuals with the Firmicutes-enriched enterotype. Constipation was lowest and subthreshold parkinsonism least frequent in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical activity, possible RBD, smoking, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history, and the prodromal PD probability showed no significant microbiome associations.

Interpretation: Several risk and prodromal markers of PD are associated with gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases. ANN NEUROL 2020;88:320-331.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.25788DOI Listing
August 2020

Skin Microbiome in Cutaneous T-Cell Lymphoma by 16S and Whole-Genome Shotgun Sequencing.

J Invest Dermatol 2020 11 28;140(11):2304-2308.e7. Epub 2020 Apr 28.

Department of Dermatology and Allergology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2020.03.951DOI Listing
November 2020

: Comparative Genomics of an Emerging Pathogen.

Int J Genomics 2020 18;2020:8708305. Epub 2020 Feb 18.

Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.

Streptococcus halichoeri is an emerging pathogen with a variety of host species and zoonotic potential. It has been isolated from grey seals and other marine mammals as well as from human infections. Beginning in 2010, two concurrent epidemics were identified in Finland, in fur animals and domestic dogs, respectively. The fur animals suffered from a new disease fur animal epidemic necrotic pyoderma (FENP) and the dogs presented with ear infections with poor treatment response. S. halichoeri was isolated in both studies, albeit among other pathogens, indicating a possible role in the disease etiologies. The aim was to find a possible common origin of the fur animal and dog isolates and study the virulence factors to assess pathogenic potential. Isolates from seal, human, dogs, and fur animals were obtained for comparison. The whole genomes were sequenced from 20 different strains using the Illumina MiSeq platform and annotated using an automatic annotation pipeline RAST. The core and pangenomes were formed by comparing the genomes against each other in an all-against-all comparison. A phylogenetic tree was constructed using the genes of the core genome. Virulence factors were assessed using the Virulence Factor Database (VFDB) concentrating on the previously confirmed streptococcal factors. A core genome was formed which encompassed approximately half of the genes in Streptococcus halichoeri. The resulting core was nearly saturated and would not change significantly by adding more genomes. The remaining genes formed the pangenome which was highly variable and would still evolve after additional genomes. The results highlight the great adaptability of this bacterium possibly explaining the ease at which it switches hosts and environments. Virulence factors were also analyzed and were found primarily in the core genome. They represented many classes and functions, but the largest single category was adhesins which again supports the marine origin of this species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8708305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049441PMC
February 2020

Red-Brown Pigmentation of Is Tied to Haemolytic Activity and Like Gene Cluster.

Microorganisms 2019 Oct 30;7(11). Epub 2019 Oct 30.

Department of Food and Nutrition, University of Helsinki, 00014 Helsinki, Finland.

The novel genus encompasses species of industrial importance but also those associated with food spoilage. In particular, , , and play an important role in food fermentation, as biopreservatives, or as potential probiotics. Notably, and can cause brown spot defects in Swiss-type cheeses, which have been tied to the rhamnolipid pigment granadaene. In the pathogenic bacterium production of granadaene depends on the presence of a gene cluster, an important virulence factor linked with haemolytic activity. Here, we show that the production of granadaene in pigmented including and , is tied to haemolytic activity and the presence of a -like gene cluster. Furthermore, we propose a PCR-based test, which allows pinpointing acidipropionibacteria with the -like gene cluster. Finally, we present the first two whole genome sequence analyses of the strains as well as testing phenotypic characteristics important for industrial applications. In conclusion, the present study sheds light on potential risks associated with the presence of pigmented strains in food fermentation. In addition, the results presented here provide ground for development of a quick and simple diagnostic test instrumental in avoiding potential negative effects of strains with haemolytic activity on food quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms7110512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920887PMC
October 2019

Multi-omics analysis identifies mitochondrial pathways associated with anxiety-related behavior.

PLoS Genet 2019 09 26;15(9):e1008358. Epub 2019 Sep 26.

Molecular and Integrative Biosciences Research Program, University of Helsinki, Helsinki, Finland.

Stressful life events are major environmental risk factors for anxiety disorders, although not all individuals exposed to stress develop clinical anxiety. The molecular mechanisms underlying the influence of environmental effects on anxiety are largely unknown. To identify biological pathways mediating stress-related anxiety and resilience to it, we used the chronic social defeat stress (CSDS) paradigm in male mice of two inbred strains, C57BL/6NCrl (B6) and DBA/2NCrl (D2), that differ in their susceptibility to stress. Using a multi-omics approach, we identified differential mRNA, miRNA and protein expression changes in the bed nucleus of the stria terminalis (BNST) and blood cells after chronic stress. Integrative gene set enrichment analysis revealed enrichment of mitochondrial-related genes in the BNST and blood of stressed mice. To translate these results to human anxiety, we investigated blood gene expression changes associated with exposure-induced panic attacks. Remarkably, we found reduced expression of mitochondrial-related genes in D2 stress-susceptible mice and in exposure-induced panic attacks in humans, but increased expression of these genes in B6 stress-susceptible mice. Moreover, stress-susceptible vs. stress-resilient B6 mice displayed more mitochondrial cross-sections in the post-synaptic compartment after CSDS. Our findings demonstrate mitochondrial-related alterations in gene expression as an evolutionarily conserved response in stress-related behaviors and validate the use of cross-species approaches in investigating the biological mechanisms underlying anxiety disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1008358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762065PMC
September 2019

gapFinisher: A reliable gap filling pipeline for SSPACE-LongRead scaffolder output.

PLoS One 2019 9;14(9):e0216885. Epub 2019 Sep 9.

DNA Sequencing and Genomics Laboratory, Institute of Biotechnology, University of Helsinki, Helsinki, Finland.

Unknown sequences, or gaps, are present in many published genomes across public databases. Gap filling is an important finishing step in de novo genome assembly, especially in large genomes. The gap filling problem is nontrivial and while there are many computational tools partially solving the problem, several have shortcomings as to the reliability and correctness of the output, i.e. the gap filled draft genome. SSPACE-LongRead is a scaffolding tool that utilizes long reads from multiple third-generation sequencing platforms in finding links between contigs and combining them. The long reads potentially contain sequence information to fill the gaps created in the scaffolding, but SSPACE-LongRead currently lacks this functionality. We present an automated pipeline called gapFinisher to process SSPACE-LongRead output to fill gaps after the scaffolding. gapFinisher is based on the controlled use of a previously published gap filling tool FGAP and works on all standard Linux/UNIX command lines. We compare the performance of gapFinisher against two other published gap filling tools PBJelly and GMcloser. We conclude that gapFinisher can fill gaps in draft genomes quickly and reliably. In addition, the serial design of gapFinisher makes it scale well from prokaryote genomes to larger genomes with no increase in the computational footprint.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216885PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733440PMC
March 2020

Cloning of novel bacterial xylanases from lignocellulose-enriched compost metagenomic libraries.

AMB Express 2019 Aug 5;9(1):124. Epub 2019 Aug 5.

VTT Technical Research Centre of Finland, P.O. Box 1000, 02044, Vuorimiehentie, Espoo, Finland.

Xylanases are in important class of industrial enzymes that are essential for the complete hydrolysis of lignocellulosic biomass into fermentable sugars. In the present study, we report the cloning of novel xylanases with interesting properties from compost metagenomics libraries. Controlled composting of lignocellulosic materials was used to enrich the microbial population in lignocellulolytic organisms. DNA extracted from the compost samples was used to construct metagenomics libraries, which were screened for xylanase activity. In total, 40 clones exhibiting xylanase activity were identified and the thermostability of the discovered xylanases was assayed directly from the library clones. Five genes, including one belonging to the more rare family GH8, were selected for subcloning and the enzymes were expressed in recombinant form in E. coli. Preliminary characterization of the metagenome-derived xylanases revealed interesting properties of the novel enzymes, such as high thermostability and specific activity, and differences in hydrolysis profiles. One enzyme was found to perform better than a standard Trichoderma reesei xylanase in the hydrolysis of lignocellulose at elevated temperatures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13568-019-0847-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682842PMC
August 2019

Phenotypic effects of dietary stress in combination with a respiratory chain bypass in mice.

Physiol Rep 2019 08;7(13):e14159

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

The alternative oxidase (AOX) from Ciona intestinalis was previously shown to be expressible in mice and to cause no physiological disturbance under unstressed conditions. Because AOX is known to become activated under some metabolic stress conditions, resulting in altered energy balance, we studied its effects in mice subjected to dietary stress. Wild-type mice (Mus musculus, strain C57BL/6JOlaHsd) fed a high-fat or ketogenic (high-fat, low-carbohydrate) diet show weight gain with increased fat mass, as well as loss of performance, compared with chow-fed animals. Unexpectedly, AOX-expressing mice fed on these metabolically stressful, fat-rich diets showed almost indistinguishable patterns of weight gain and altered body composition as control animals. Cardiac performance was impaired to a similar extent by ketogenic diet in AOX mice as in nontransgenic littermates. AOX and control animals fed on ketogenic diet both showed wide variance in weight gain. Analysis of the gut microbiome in stool revealed a strong correlation with diet, rather than with genotype. The microbiome of the most and least obese outliers reared on the ketogenic diet showed no consistent trends compared with animals of normal body weight. We conclude that AOX expression in mice does not modify physiological responses to extreme diets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14814/phy2.14159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606514PMC
August 2019

Gut microbiota in Parkinson's disease: Temporal stability and relations to disease progression.

EBioMedicine 2019 Jun 18;44:691-707. Epub 2019 Jun 18.

Department of Neurology, Helsinki University Hospital, and Department of Neurological Sciences (Neurology), University of Helsinki, Haartmaninkatu 4, 00290 Helsinki, Finland. Electronic address:

Background: Several publications have described differences in cross-sectional comparisons of gut microbiota between patients with Parkinson's disease and control subjects, with considerable variability of the reported differentially abundant taxa. The temporal stability of such microbiota alterations and their relationship to disease progression have not been previously studied with a high-throughput sequencing based approach.

Methods: We collected clinical data and stool samples from 64 Parkinson's patients and 64 control subjects twice, on average 2·25 years apart. Disease progression was evaluated based on changes in Unified Parkinson's Disease Rating Scale and Levodopa Equivalent Dose, and microbiota were characterized with 16S rRNA gene amplicon sequencing.

Findings: We compared patients to controls, and patients with stable disease to those with faster progression. There were significant differences between microbial communities of patients and controls when corrected for confounders, but not between timepoints. Specific bacterial taxa that differed between patients and controls at both timepoints included several previously reported ones, such as Roseburia, Prevotella and Bifidobacterium. In progression comparisons, differentially abundant taxa were inconsistent across methods and timepoints, but there was some support for a different distribution of enterotypes and a decreased abundance of Prevotella in faster-progressing patients.

Interpretation: The previously detected gut microbiota differences between Parkinson's patients and controls persisted after 2 years. While we found some evidence for a connection between microbiota and disease progression, a longer follow-up period is required to confirm these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2019.05.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606744PMC
June 2019

Genome description of Phlebia radiata 79 with comparative genomics analysis on lignocellulose decomposition machinery of phlebioid fungi.

BMC Genomics 2019 May 28;20(1):430. Epub 2019 May 28.

Department of Microbiology, Faculty of Agriculture and Forestry, Viikki Campus, University of Helsinki, FI-00014, Helsinki, Finland.

Background: The white rot fungus Phlebia radiata, a type species of the genus Phlebia, is an efficient decomposer of plant cell wall polysaccharides, modifier of softwood and hardwood lignin, and is able to produce ethanol from various waste lignocellulose substrates. Thus, P. radiata is a promising organism for biotechnological applications aiming at sustainable utilization of plant biomass. Here we report the genome sequence of P. radiata isolate 79 originally isolated from decayed alder wood in South Finland. To better understand the evolution of wood decay mechanisms in this fungus and the Polyporales phlebioid clade, gene content and clustering of genes encoding specific carbohydrate-active enzymes (CAZymes) in seven closely related fungal species was investigated. In addition, other genes encoding proteins reflecting the fungal lifestyle including peptidases, transporters, small secreted proteins and genes involved in secondary metabolism were identified in the genome assembly of P. radiata.

Results: The PACBio sequenced nuclear genome of P. radiata was assembled to 93 contigs with 72X sequencing coverage and annotated, revealing a dense genome of 40.4 Mbp with approximately 14 082 predicted protein-coding genes. According to functional annotation, the genome harbors 209 glycoside hydrolase, 27 carbohydrate esterase, 8 polysaccharide lyase, and over 70 auxiliary redox enzyme-encoding genes. Comparisons with the genomes of other phlebioid fungi revealed shared and specific properties among the species with seemingly similar saprobic wood-decay lifestyles. Clustering of especially GH10 and AA9 enzyme-encoding genes according to genomic localization was discovered to be conserved among the phlebioid species. In P. radiata genome, a rich repertoire of genes involved in the production of secondary metabolites was recognized. In addition, 49 genes encoding predicted ABC proteins were identified in P. radiata genome together with 336 genes encoding peptidases, and 430 genes encoding small secreted proteins.

Conclusions: The genome assembly of P. radiata contains wide array of carbohydrate polymer attacking CAZyme and oxidoreductase genes in a composition identifiable for phlebioid white rot lifestyle in wood decomposition, and may thus serve as reference for further studies. Comparative genomics also contributed to enlightening fungal decay mechanisms in conversion and cycling of recalcitrant organic carbon in the forest ecosystems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-019-5817-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540522PMC
May 2019

Bracketing phenogenotypic limits of mammalian hybridization.

R Soc Open Sci 2018 Nov 28;5(11):180903. Epub 2018 Nov 28.

Developmental Biology Program, Institute of Biotechnology, University of Helsinki, PO Box 56, 00014 Helsinki, Finland.

An increasing number of mammalian species have been shown to have a history of hybridization and introgression based on genetic analyses. Only relatively few fossils, however, preserve genetic material, and morphology must be used to identify the species and determine whether morphologically intermediate fossils could represent hybrids. Because dental and cranial fossils are typically the key body parts studied in mammalian palaeontology, here we bracket the potential for phenotypically extreme hybridizations by examining uniquely preserved cranio-dental material of a captive hybrid between grey and ringed seals. We analysed how distinct these species are genetically and morphologically, how easy it is to identify the hybrids using morphology and whether comparable hybridizations happen in the wild. We show that the genetic distance between these species is more than twice the modern human-Neanderthal distance, but still within that of morphologically similar species pairs known to hybridize. By contrast, morphological and developmental analyses show grey and ringed seals to be highly disparate, and that the hybrid is a predictable intermediate. Genetic analyses of the parent populations reveal introgression in the wild, suggesting that grey-ringed seal hybridization is not limited to captivity. Taken together, we postulate that there is considerable potential for mammalian hybridization between phenotypically disparate taxa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1098/rsos.180903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281900PMC
November 2018
-->