Effects of the 2014 major Baltic inflow on methane and nitrous oxide dynamics in the water column of the Central Baltic Sea

Peer reviewe

Primary familial brain calcification linked to deletion of 5' noncoding region of SLC20A2

OBJECTIVES: Primary familial brain calcification (PFBC) is a rare neurological disease often inherited as a dominant trait. Mutations in four genes (SLC20A2, PDGFB, PDGFRB, and XPR1) have been reported in patients with PFBC. Of these, point mutations or small deletions in SLC20A2 are most common. Thus far, only one large deletion covering entire SLC20A2 and several smaller, exonic deletions of SLC20A2 have been reported. The aim of this study was to identify the causative gene defect in a Finnish PFBC family with three affected patients. MATERIALS AND METHODS: A Finnish family with three PFBC patients and five unaffected subjects was studied. Sanger sequencing was used to exclude mutations in the coding and splice site regions of SLC20A2, PDGFRB, and PDGFB. Whole-exome (WES) and whole-genome sequencing (WGS) were performed to identify the causative mutation. A SNP array was used in segregation analysis. RESULTS: Copy number analysis of the WGS data revealed a heterozygous deletion of ~578 kb on chromosome 8. The deletion removes the 5' UTR region, the noncoding exon 1 and the putative promoter region of SLC20A2 as well as the coding regions of six other genes. CONCLUSIONS: Our results support haploinsufficiency of SLC20A2 as a pathogenetic mechanism in PFBC. Analysis of copy number variations (CNVs) is emerging as a crucial step in the molecular genetic diagnostics of PFBC, and it should not be limited to coding regions, as causative variants may reside in the noncoding parts of known disease-associated genes

From clear lakes to murky waters - tracing the functional response of high-latitude lake communities to concurrent 'greening' and 'browning'

Climate change and the intensification of land use practices are causing widespread eutrophication of subarctic lakes. The implications of this rapid change for lake ecosystem function remain poorly understood. To assess how freshwater communities respond to such profound changes in their habitat and resource availability, we conducted a space-for-time analysis of food-web structure in 30 lakes situated across a temperature-productivity gradient equivalent to the predicted future climate of subarctic Europe (temperature +3 degrees C, precipitation +30% and nutrient +45 mu g L-1 total phosphorus). Along this gradient, we observed an increase in the assimilation of pelagic-derived carbon from 25 to 75% throughout primary, secondary and tertiary consumers. This shift was overwhelmingly driven by the consumption of pelagic detritus by benthic primary consumers and was not accompanied by increased pelagic foraging by higher trophic level consumers. Our data also revealed a convergence of the carbon isotope ratios of pelagic and benthic food web endmembers in the warmest, most productive lakes indicating that the incorporation of terrestrial derived carbon into aquatic food webs increases as land use intensifies. These results, reflecting changes along a gradient characteristic of the predicted future environment throughout the subarctic, indicate that climate and land use driven eutrophication and browning are radically altering the function and fuelling of aquatic food webs in this biome.Peer reviewe

Comparative genomics and genome biology of invasive Campylobacter jejuni

Campylobacter jejuni is a major pathogen in bacterial gastroenteritis worldwide and can cause bacteremia in severe cases. C. jejuni is highly structured into clonal lineages of which the ST677CC lineage has been overrepresented among C. jejuni isolates derived from blood. In this study, we characterized the genomes of 31 C. jejuni blood isolates and 24 faecal isolates belonging to ST677CC in order to study the genome biology related to C. jejuni invasiveness. We combined the genome analyses with phenotypical evidence on serum resistance which was associated with phase variation of wcbK; a GDP-mannose 4,6-dehydratase involved in capsular biosynthesis. We also describe the finding of a Type III restriction-modification system unique to the ST-794 sublineage. However, features previously considered to be related to pathogenesis of C. jejuni were either absent or disrupted among our strains. Our results refine the role of capsule features associated with invasive disease and accentuate the possibility of methylation and restriction enzymes in the potential of C. jejuni to establish invasive infections. Our findings underline the importance of studying clinically relevant well-characterized bacterial strains in order to understand pathogenesis mechanisms important in human infections.Peer reviewe

A new method for estimating carbon dioxide emissions from drained peatland forest soils for the greenhouse gas inventory of Finland

In peatlands drained for forestry, the soil carbon (C) or carbon dioxide (CO2) balance is affected by both (i) higher heterotrophic CO2-C release from faster decomposing soil organic matter (SOM) and (ii) higher plant litter C input from more vigorously growing forests. This balance and other greenhouse gas (GHG) sinks and sources in managed lands are annually reported by national GHG inventories to the United Nations Climate Change Convention. In this paper, we present a revised, fully dynamic method for reporting the CO2 balance of drained peatland forest soils in Finland. Our method can follow temporal changes in tree biomass growth, tree harvesting and climatic parameters, and it is built on empirical regression models of SOM decomposition and litter input in drained peatland forests. All major components of aboveground and belowground litter input from ground vegetation as well as live trees and trees that died naturally are included, supplemented by newly acquired turnover rates of woody plant fine roots. Annual litter input from harvesting residues is calculated using national statistics of logging and energy use of trees. Leaching, which also exports dissolved C from drained peatlands, is not included. The results are reported as time series from 1990–2021 following the practice in the GHG inventory. Our revised method produces an increasing trend of annual emissions from 0.2 to 2.1 t CO2 ha−1 yr−1 for the period 1990–2021 in Finland (equal to a trend from 1.4 to 7.9 Mt CO2 yr−1 for the entire 4.3 Mha of drained peatland forests), with a statistically significant difference between the years 1990 and 2021. Across the period 1990–2021, annual emissions are on average 1.5 t CO2 ha−1 yr−1 (3.4 Mt CO2 yr−1 for 2.2 Mha area) in warmer southern Finland and −0.14 t CO2 ha−1 yr−1 (−0.3 Mt CO2 yr−1 for 2.1 Mha area) in cooler northern Finland. When combined with data on the CO2 sink created by the growing tree stock, in 2021 the drained peatland forest ecosystems were a source of 1.0 t CO2 ha−1 yr−1 (2.3 Mt CO2 yr−1) in southern Finland and a sink of 1.2 t CO2 ha−1 yr−1 (2.5 Mt CO2 yr−1) in northern Finland. We compare these results to those produced by the semi-dynamic method used earlier in the Finnish GHG inventory and discuss the strengths and vulnerabilities of the new revised method in comparison to more static emission factors.</p

An algorithm for classifying tumors based on genomic aberrations and selecting representative tumor models

<p>Abstract</p> <p>Background</p> <p>Cancer is a heterogeneous disease caused by genomic aberrations and characterized by significant variability in clinical outcomes and response to therapies. Several subtypes of common cancers have been identified based on alterations of individual cancer genes, such as HER2, EGFR, and others. However, cancer is a complex disease driven by the interaction of multiple genes, so the copy number status of individual genes is not sufficient to define cancer subtypes and predict responses to treatments. A classification based on genome-wide copy number patterns would be better suited for this purpose.</p> <p>Method</p> <p>To develop a more comprehensive cancer taxonomy based on genome-wide patterns of copy number abnormalities, we designed an unsupervised classification algorithm that identifies genomic subgroups of tumors. This algorithm is based on a modified genomic Non-negative Matrix Factorization (gNMF) algorithm and includes several additional components, namely a pilot hierarchical clustering procedure to determine the number of clusters, a multiple random initiation scheme, a new stop criterion for the core gNMF, as well as a 10-fold cross-validation stability test for quality assessment.</p> <p>Result</p> <p>We applied our algorithm to identify genomic subgroups of three major cancer types: non-small cell lung carcinoma (NSCLC), colorectal cancer (CRC), and malignant melanoma. High-density SNP array datasets for patient tumors and established cell lines were used to define genomic subclasses of the diseases and identify cell lines representative of each genomic subtype. The algorithm was compared with several traditional clustering methods and showed improved performance. To validate our genomic taxonomy of NSCLC, we correlated the genomic classification with disease outcomes. Overall survival time and time to recurrence were shown to differ significantly between the genomic subtypes.</p> <p>Conclusions</p> <p>We developed an algorithm for cancer classification based on genome-wide patterns of copy number aberrations and demonstrated its superiority to existing clustering methods. The algorithm was applied to define genomic subgroups of three cancer types and identify cell lines representative of these subgroups. Our data enabled the assembly of representative cell line panels for testing drug candidates.</p

Relevance of Titin Missense and Non-Frameshifting Insertions/Deletions Variants in Dilated Cardiomyopathy

Recent advancements in next generation sequencing (NGS) technology have led to the identification of the giant sarcomere gene, titin (TTN), as a major human disease gene. Truncating variants of TTN (TTNtv) especially in the A-band region account for 20% of dilated cardiomyopathy (DCM) cases. Much attention has been focused on assessment and interpretation of TTNtv in human disease; however, missense and non-frameshifting insertions/deletions (NFS-INDELs) are difficult to assess and interpret in clinical diagnostic workflow. Targeted sequencing covering all exons of TTN was performed on a cohort of 530 primary DCM patients from three cardiogenetic centres across Europe. Using stringent bioinformatic filtering, twenty-nine and two rare TTN missense and NFS-INDELs variants predicted deleterious were identified in 6.98% and 0.38% of DCM patients, respectively. However, when compared with those identified in the largest available reference population database, no significant enrichment of such variants was identified in DCM patients. Moreover, DCM patients and reference individuals had comparable frequencies of splice-region missense variants with predicted splicing alteration. DCM patients and reference populations had comparable frequencies of rare predicted deleterious TTN missense variants including splice-region missense variants suggesting that these variants are not independently causative for DCM. Hence, these variants should be classified as likely benign in the clinical diagnostic workflow, although a modifier effect cannot be excluded at this stage.Peer reviewe

Publisher Correction:Relevance of Titin Missense and Non-Frameshifting Insertions/Deletions Variants in Dilated Cardiomyopathy

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Genetics of dementia in a Finnish cohort.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the two most common neurodegenerative dementias. Variants in APP, PSEN1 and PSEN2 are typically linked to early-onset AD, and several genetic risk loci are associated with late-onset AD. Inherited FTD can be caused by hexanucleotide expansions in C9orf72, or variants in GRN, MAPT or CHMP2B. Several other genes have also been linked to FTD or FTD with motor neuron disease. Here we describe a cohort of 60 Finnish families with possible inherited dementia. Our aim was to clarify the genetic background of dementia in this cohort by analysing both known dementia-associated genes (APOE, APP, C9ORF72, GRN, PSEN1 and PSEN2) and searching for rare or novel segregating variants with exome sequencing. C9orf72 repeat expansions were detected in 12 (20%) of the 60 families, including, in addition to FTD, a family with neuropathologically verified AD. Twelve families (10 with AD and 2 with FTD) with representative samples from affected and unaffected subjects and without C9orf72 expansions were selected for whole-exome sequencing. Exome sequencing did not reveal any variants that could be regarded unequivocally causative, but revealed potentially damaging variants in UNC13C and MARCH4