Publications by authors named "Petri Auvinen"

143 Publications

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

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

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

Microbiome of the Healthy External Auditory Canal.

Otol Neurotol 2020 Dec 17;Publish Ahead of Print. Epub 2020 Dec 17.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital Institute of Biotechnology, HiLIFE, Helsinki Institute of Life Science, University of Helsinki Department of Neurology, Helsinki University Hospital, Helsinki, Finland Department of Otorhinolaryngology, Akershus University Hospital and University of Oslo, Akershus and Oslo, Norway.

Objective: To investigate the microbiota of the healthy external auditory canal (EAC) culture-independently and to evaluate the usefulness of the swabbing method in collecting EAC microbiota samples.

Study Design: Cohort study.

Patients: Fifty healthy asymptomatic working-age volunteers.

Intervention: Samples were harvested with DNA-free swabs from the volunteers' EACs.

Main Outcome Measures: Amplicon sequencing of the 16S rRNA gene was used to characterize the microbial communities in the samples.

Results: The swabbing method is feasible for EAC microbiota sample collection. The analyzed 41 samples came from 27 female and 14 male subjects; 4 samples were excluded due to recent antimicrobial treatment and 5 because of low sequence count or suspected contaminant microbes. The four most frequent amplicon sequence variants in the microbiota data were Staphylococcus auricularis, Propionibacterium acnes, Alloiococcus otitis, and Turicella otitidis. Typically, the dominant amplicon sequence variant in a sample was one of the most frequent bacteria, but there were also subjects where the dominant species was not among the most frequent ones. The genus Alloiococcus was least common in females who reported cleaning their ears. Subjects with a high relative abundance of Alloiococcus typically had a low abundance of Staphylococcus, which may be a sign of the two being competing members of the microbial community.

Conclusions: The most common bacteria in the microbiome of the healthy EAC were Staphylococcus auricularis, Propionibacterium acnes, Alloiococcus otitis, and Turicella otitidis. The EAC microbiota seems more diverse and individualized than previously thought. Also, ear cleaning habits seem to alter the EAC microbiome.
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http://dx.doi.org/10.1097/MAO.0000000000003031DOI Listing
December 2020

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

Genomic characterization of the most barotolerant Listeria monocytogenes RO15 strain compared to reference strains used to evaluate food high pressure processing.

BMC Genomics 2020 Jul 2;21(1):455. Epub 2020 Jul 2.

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

Background: High pressure processing (HPP; i.e. 100-600 MPa pressure depending on product) is a non-thermal preservation technique adopted by the food industry to decrease significantly foodborne pathogens, including Listeria monocytogenes, from food. However, susceptibility towards pressure differs among diverse strains of L. monocytogenes and it is unclear if this is due to their intrinsic characteristics related to genomic content. Here, we tested the barotolerance of 10 different L. monocytogenes strains, from food and food processing environments and widely used reference strains including clinical isolate, to pressure treatments with 400 and 600 MPa. Genome sequencing and genome comparison of the tested L. monocytogenes strains were performed to investigate the relation between genomic profile and pressure tolerance.

Results: None of the tested strains were tolerant to 600 MPa. A reduction of more than 5 log was observed for all strains after 1 min 600 MPa pressure treatment. L. monocytogenes strain RO15 showed no significant reduction in viable cell counts after 400 MPa for 1 min and was therefore defined as barotolerant. Genome analysis of so far unsequenced L. monocytogenes strain RO15, 2HF33, MB5, AB199, AB120, C7, and RO4 allowed us to compare the gene content of all strains tested. This revealed that the three most pressure tolerant strains had more than one CRISPR system with self-targeting spacers. Furthermore, several anti-CRISPR genes were detected in these strains. Pan-genome analysis showed that 10 prophage genes were significantly associated with the three most barotolerant strains.

Conclusions: L. monocytogenes strain RO15 was the most pressure tolerant among the selected strains. Genome comparison suggests that there might be a relationship between prophages and pressure tolerance in L. monocytogenes.
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http://dx.doi.org/10.1186/s12864-020-06819-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331262PMC
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.
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http://dx.doi.org/10.3233/JND-200523DOI Listing
January 2020

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

Dual-light photodynamic therapy administered daily provides a sustained antibacterial effect on biofilm and prevents Streptococcus mutans adaptation.

PLoS One 2020 6;15(5):e0232775. Epub 2020 May 6.

Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland.

Antibacterial photodynamic therapy (aPDT) and antibacterial blue light (aBL) are emerging treatment methods auxiliary to mechanical debridement for periodontitis. APDT provided with near-infrared (NIR) light in conjunction with an indocyanine green (ICG) photosensitizer has shown efficacy in several dental in-office-treatment protocols. In this study, we tested Streptococcus mutans biofilm sensitivity to either aPDT, aBL or their combination dual-light aPDT (simultaneous aPDT and aBL) exposure. Biofilm was cultured by pipetting diluted Streptococcus mutans suspension with growth medium on the bottom of well plates. Either aPDT (810 nm) or aBL (405 nm) or a dual-light aPDT (simultaneous 810 nm aPDT and 405 nm aBL) was applied with an ICG photosensitizer in cases of aPDT or dual-light, while keeping the total given radiant exposure constant at 100 J/cm2. Single-dose light exposures were given after one-day or four-day biofilm incubations. Also, a model of daily treatment was provided by repeating the same light dose daily on four-day and fourteen-day biofilm incubations. Finally, the antibacterial action of the dual-light aPDT with different energy ratios of 810 nm and 405 nm of light were examined on the single-day and four-day biofilm protocols. At the end of each experiment the bacterial viability was assessed by colony-forming unit method. Separate samples were prepared for confocal 3D biofilm imaging. On a one-day biofilm, the dual-light aPDT was significantly more efficient than aBL or aPDT, although all modalities were bactericidal. On a four-day biofilm, a single exposure of aPDT or dual-light aPDT was more efficient than aBL, resulting in a four logarithmic scale reduction in bacterial counts. Surprisingly, when the same amount of aPDT was repeated daily on a four-day or a fourteen-day biofilm, bacterial viability improved significantly. A similar improvement in bacterial viability was observed after repetitive aBL application. This viability improvement was eliminated when dual-light aPDT was applied. By changing the 405 nm to 810 nm radiant exposure ratio in dual-light aPDT, the increase in aBL improved the antibacterial action when the biofilm was older. In conclusion, when aPDT is administered repeatedly to S. mutans biofilm, a single wavelength-based aBL or aPDT leads to a significant biofilm adaptation and increased S. mutans viability. The combined use of aBL light in synchrony with aPDT arrests the adaptation and provides significantly improved and sustained antibacterial efficacy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232775PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202659PMC
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.

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http://dx.doi.org/10.1016/j.jid.2020.03.951DOI Listing
November 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.
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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.
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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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216885PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733440PMC
March 2020

Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium.

Nature 2019 07 10;571(7765):398-402. Epub 2019 Jul 10.

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

A decline in stem cell function impairs tissue regeneration during ageing, but the role of the stem-cell-supporting niche in ageing is not well understood. The small intestine is maintained by actively cycling intestinal stem cells that are regulated by the Paneth cell niche. Here we show that the regenerative potential of human and mouse intestinal epithelium diminishes with age owing to defects in both stem cells and their niche. The functional decline was caused by a decrease in stemness-maintaining Wnt signalling due to production of Notum, an extracellular Wnt inhibitor, in aged Paneth cells. Mechanistically, high activity of mammalian target of rapamycin complex 1 (mTORC1) in aged Paneth cells inhibits activity of peroxisome proliferator activated receptor α (PPAR-α), and lowered PPAR-α activity increased Notum expression. Genetic targeting of Notum or Wnt supplementation restored function of aged intestinal organoids. Moreover, pharmacological inhibition of Notum in mice enhanced the regenerative capacity of aged stem cells and promoted recovery from chemotherapy-induced damage. Our results reveal a role of the stem cell niche in ageing and demonstrate that targeting of Notum can promote regeneration of aged tissues.
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http://dx.doi.org/10.1038/s41586-019-1383-0DOI Listing
July 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.
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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.
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http://dx.doi.org/10.1016/j.ebiom.2019.05.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606744PMC
June 2019

Author Correction: Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch.

Nat Genet 2019 Jul;51(7):1187-1189

Division of Plant Biology, Department of Biosciences, University of Helsinki, Helsinki, Finland.

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http://dx.doi.org/10.1038/s41588-019-0442-7DOI Listing
July 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.
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http://dx.doi.org/10.1186/s12864-019-5817-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540522PMC
May 2019

Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED.

Endocr Connect 2019 Jan;8(1):69-77

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

Objective Intestinal autoimmunity with gastrointestinal (GI) dysfunction has been shown in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Patients lack entero-endocrine (EE) cells and have circulating autoantibodies (Aabs) against critical enzymes in serotonin (5-HT) biosynthesis. Design We sought to determine the serum levels of 5-HT, tryptophan (Trp) metabolites and L-DOPA in 37 Finnish APECED patients and to correlate their abundance with the presence of TPH and AADC Aabs, GI dysfunction and depressive symptoms. We also performed an exploratory analysis of the gut microbiome. Methods Serum 5-HT, L-DOPA and Trp metabolite levels were determined by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). TPH and AADC Aabs were measured by ELISA. Depression was assessed with a structured RBDI questionnaire. The V3-V4 regions of the bacterial 16S rRNA gene were sequenced for gut microbiome exploration. Results Serum 5-HT levels were significantly decreased (130 ± 131 nmol/L vs 686 ± 233 nmol/L, P < 0.0001) in APECED patients with TPH-1 (±AADC) Aabs compared to controls and patients with only AADC Aabs. Reduced 5-HT levels correlated with constipation. The genus Escherichia/Shigella was overrepresented in the intestinal microbiome. No correlation between serum Trp, 5-HT or l-DOPA levels and the RBDI total score, fatigue or sleep disorders was found. Conclusions This exploratory study found low serum levels of 5-HT to be associated with constipation and the presence of TPH-1 and AADC Aabs, but not with symptoms of depression. Hence, serum 5-HT, TPH1 and AADC Aabs should be determined in APECED patients presenting with GI symptoms.
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http://dx.doi.org/10.1530/EC-18-0513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365670PMC
January 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.
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http://dx.doi.org/10.1098/rsos.180903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281900PMC
November 2018

Alternative oxidase-mediated respiration prevents lethal mitochondrial cardiomyopathy.

EMBO Mol Med 2019 01;11(1)

Folkhälsan Research Center, Helsinki, Finland

Alternative oxidase (AOX) is a non-mammalian enzyme that can bypass blockade of the complex III-IV segment of the respiratory chain (RC). We crossed a AOX transgene into RC complex III (cIII)-deficient knock-in mice, displaying multiple visceral manifestations and premature death. The homozygotes expressing AOX were viable, and their median survival was extended from 210 to 590 days due to permanent prevention of lethal cardiomyopathy. AOX also prevented renal tubular atrophy and cerebral astrogliosis, but not liver disease, growth restriction, or lipodystrophy, suggesting distinct tissue-specific pathogenetic mechanisms. Assessment of reactive oxygen species (ROS) production and damage suggested that ROS were not instrumental in the rescue. Cardiac mitochondrial ultrastructure, mitochondrial respiration, and pathological transcriptome and metabolome alterations were essentially normalized by AOX, showing that the restored electron flow upstream of cIII was sufficient to prevent cardiac energetic crisis and detrimental decompensation. These findings demonstrate the value of AOX, both as a mechanistic tool and a potential therapeutic strategy, for cIII deficiencies.
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http://dx.doi.org/10.15252/emmm.201809456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328925PMC
January 2019

The Receptor-like Pseudokinase GHR1 Is Required for Stomatal Closure.

Plant Cell 2018 11 25;30(11):2813-2837. Epub 2018 Oct 25.

Organismal and Evolutionary Biology Research Programme, Faculty of Biological and Environmental Sciences, and Viikki Plant Science Centre, University of Helsinki, FI-00014 Helsinki, Finland

Guard cells control the aperture of stomatal pores to balance photosynthetic carbon dioxide uptake with evaporative water loss. Stomatal closure is triggered by several stimuli that initiate complex signaling networks to govern the activity of ion channels. Activation of SLOW ANION CHANNEL1 (SLAC1) is central to the process of stomatal closure and requires the leucine-rich repeat receptor-like kinase (LRR-RLK) GUARD CELL HYDROGEN PEROXIDE-RESISTANT1 (GHR1), among other signaling components. Here, based on functional analysis of nine mutant alleles identified in two independent forward-genetic ozone-sensitivity screens, we found that GHR1 is required for stomatal responses to apoplastic reactive oxygen species, abscisic acid, high CO concentrations, and diurnal light/dark transitions. Furthermore, we show that the amino acid residues of GHR1 involved in ATP binding are not required for stomatal closure in Arabidopsis or the activation of SLAC1 anion currents in oocytes and present supporting in silico and in vitro evidence suggesting that GHR1 is an inactive pseudokinase. Biochemical analyses suggested that GHR1-mediated activation of SLAC1 occurs via interacting proteins and that CALCIUM-DEPENDENT PROTEIN KINASE3 interacts with GHR1. We propose that GHR1 acts in stomatal closure as a scaffolding component.
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http://dx.doi.org/10.1105/tpc.18.00441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305979PMC
November 2018

Acidipropionibacterium virtanenii sp. nov., isolated from malted barley.

Int J Syst Evol Microbiol 2018 Oct 29;68(10):3175-3183. Epub 2018 Aug 29.

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

A Gram-stain-positive, catalase-positive and pleomorphic rod organism was isolated from malted barley in Finland, classified initially by partial 16S rRNA gene sequencing and originally deposited in the VTT Culture Collection as a strain of Propionibacterium acidipropionici (currently Acidipropionibacterium acidipropionici). The subsequent comparison of the whole 16S rRNA gene with other representatives of the genus Acidipropionibacterium revealed that the strain belongs to a novel species, most closely related to Acidipropionibacterium microaerophilum and Acidipropionibacterium acidipropionici, with similarity values of 98.46 and 98.31 %, respectively. The whole genome sequencing using PacBio RS II platform allowed further comparison of the genome with all of the other DNA sequences available for the type strains of the Acidipropionibacterium species. Those comparisons revealed the highest similarity of strain JS278 to A. acidipropionici, which was confirmed by the average nucleotide identity analysis. The genome of strain JS278 is intermediate in size compared to the A. acidipropionici and Acidipropionibacterium jensenii at 3 432 872 bp, the G+C content is 68.4 mol%. The strain fermented a wide range of carbon sources, and produced propionic acid as the major fermentation product. Besides its poor ability to grow at 37 °C and positive catalase reaction, the observed phenotype was almost indistinguishable from those of A. acidipropionici and A. jensenii. Based on our findings, we conclude that the organism represents a novel member of the genus Acidipropionibacterium, for which we propose the name Acidipropionibacteriumvirtanenii sp. nov. The type strain is JS278 (=VTT E-113202=DSM 106790).
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http://dx.doi.org/10.1099/ijsem.0.002965DOI Listing
October 2018

Genetic Control of Myelin Plasticity after Chronic Psychosocial Stress.

eNeuro 2018 Jul-Aug;5(4). Epub 2018 Jul 11.

Molecular and Integrative Biosciences Research Program, University of Helsinki, Helsinki FI-00014, Finland.

Anxiety disorders often manifest in genetically susceptible individuals after psychosocial stress, but the mechanisms underlying these gene-environment interactions are largely unknown. We used the chronic social defeat stress (CSDS) mouse model to study resilience and susceptibility to chronic psychosocial stress. We identified a strong genetic background effect in CSDS-induced social avoidance (SA) using four inbred mouse strains: 69% of C57BL/6NCrl (B6), 23% of BALB/cAnNCrl, 19% of 129S2/SvPasCrl, and 5% of DBA/2NCrl (D2) mice were stress resilient. Furthermore, different inbred mouse strains responded differently to stress, suggesting they use distinct coping strategies. To identify biological pathways affected by CSDS, we used RNA-sequencing (RNA-seq) of three brain regions of two strains, B6 and D2: medial prefrontal cortex (mPFC), ventral hippocampus (vHPC), and bed nucleus of the stria terminalis (BNST). We discovered overrepresentation of oligodendrocyte (OLG)-related genes in the differentially expressed gene population. Because OLGs myelinate axons, we measured myelin thickness and found significant region and strain-specific differences. For example, in resilient D2 mice, mPFC axons had thinner myelin than controls, whereas susceptible B6 mice had thinner myelin than controls in the vHPC. Neither myelin-related gene expression in several other regions nor corpus callosum thickness differed between stressed and control animals. Our unbiased gene expression experiment suggests that myelin plasticity is a substantial response to chronic psychosocial stress, varies across brain regions, and is genetically controlled. Identification of genetic regulators of the myelin response will provide mechanistic insight into the molecular basis of stress-related diseases, such as anxiety disorders, a critical step in developing targeted therapy.
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http://dx.doi.org/10.1523/ENEURO.0166-18.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071195PMC
March 2019

BARCOSEL: a tool for selecting an optimal barcode set for high-throughput sequencing.

BMC Bioinformatics 2018 07 5;19(1):257. Epub 2018 Jul 5.

DNA Sequencing and Genomics Laboratory, Institute of Biotechnology, FIN-00014 University of Helsinki, P.O.Box 56, Finland.

Background: Current high-throughput sequencing platforms provide capacity to sequence multiple samples in parallel. Different samples are labeled by attaching a short sample specific nucleotide sequence, barcode, to each DNA molecule prior pooling them into a mix containing a number of libraries to be sequenced simultaneously. After sequencing, the samples are binned by identifying the barcode sequence within each sequence read. In order to tolerate sequencing errors, barcodes should be sufficiently apart from each other in sequence space. An additional constraint due to both nucleotide usage and basecalling accuracy is that the proportion of different nucleotides should be in balance in each barcode position. The number of samples to be mixed in each sequencing run may vary and this introduces a problem how to select the best subset of available barcodes at sequencing core facility for each sequencing run. There are plenty of tools available for de novo barcode design, but they are not suitable for subset selection.

Results: We have developed a tool which can be used for three different tasks: 1) selecting an optimal barcode set from a larger set of candidates, 2) checking the compatibility of user-defined set of barcodes, e.g. whether two or more libraries with existing barcodes can be combined in a single sequencing pool, and 3) augmenting an existing set of barcodes. In our approach the selection process is formulated as a minimization problem. We define the cost function and a set of constraints and use integer programming to solve the resulting combinatorial problem. Based on the desired number of barcodes to be selected and the set of candidate sequences given by user, the necessary constraints are automatically generated and the optimal solution can be found. The method is implemented in C programming language and web interface is available at http://ekhidna2.biocenter.helsinki.fi/barcosel .

Conclusions: Increasing capacity of sequencing platforms raises the challenge of mixing barcodes. Our method allows the user to select a given number of barcodes among the larger existing barcode set so that both sequencing errors are tolerated and the nucleotide balance is optimized. The tool is easy to access via web browser.
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http://dx.doi.org/10.1186/s12859-018-2262-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034344PMC
July 2018