Water and nitrogen processes along a typical water flowpath and streamwater exports from a forested catchment and changes after clear-cutting: a modelling study

International audienceA two dimensional model, FEMMA, to describe water and nitrogen (N) fluxes within and from a forested first-order catchment (Kangasvaara in Eastern Finland) was constructed by linking the most significant processes affecting the fluxes of water, ammonium, nitrate and dissolved organic nitrogen along a hillslope from the water divide to the stream. The hillslope represents the average flowpath of water in the catchment and the model was used to estimate the N fluxes for a catchment in eastern Finland before and after clear-cutting. The simulated results were in reasonable agreement with the nitrate, dissolved organic N and dissolved total N measurements from the study catchment and with other results in the literature. According to the simulations, the major sinks of N after clear-cutting were immobilisation by soil microbes, uptake by ground vegetation and sorption to soil. These sinks increased downslope from the clear-cut area, indicating the importance of an uncut buffer zone between the stream and the clear-cut area in reducing N exports. The buffer zone retained 76% of the N flux coming from the clear-cut area. Nitrification was a key process in controlling the N export after clear-cutting and N increases were mainly as nitrate. Most of the annual N export took place during the spring flood, when uptake of N by plants was minimal

Ophiostoma spp. associated with pine- and spruce-infesting bark beetles in Finland and Russia

The timber and pulp industries of Finland rely heavily on importations from Russia as source of raw timber. These imports raise the risk of accidentally importing forest pests and pathogens, especially bark beetles and their associated fungi, into Finland. Although ophiostomatoid fungi have previously been reported from Finland and Russia, the risks of accidentally moving these fungi has prompted a first survey to compare the diversity of conifer-infesting bark beetles and associated fungi from boreal forests on both sides of the Finnish-Russian border. The aim of the present study was to identify and characterise Ophiostoma species isolated in association with 11 bark beetle species infesting Pinus sylvestris and Picea abies during this survey in the eastern parts of Finland and neighbouring Russia. Fungal isolates were grouped based on morphology and representatives of each morphological group were subjected to DNA sequence comparisons of the internal transcribed spaced region (ITS1, 5.8S, ITS2) and β-tubulin gene region. A total of 15 species of Ophiostoma were identified, including seven known species, five new species, and three species for which the identity remains uncertain. In the O. piceae-complex we identified O. canum, O. floccosum, O. karelicum and O. rachisporum sp. nov., and related to these, some isolates belonging to the European clade of O. minus in the O. minus-complex. Ophiostoma bicolor and O. fuscum sp. nov. were identified in the O. ips-complex, while O. ainoae, O. brunneo-ciliatum, O. tapionis sp. nov. and O. pallidulum sp. nov. were shown to group close to, but not in a strict monophyletic lineage with species of the O. ips-complex. Together with a single O. abietinum-like isolate, the only species that grouped close to the Sporothrix schenckii- O. stenoceras complex, was O. saponiodorum sp. nov

Prognostic Value of Immune Environment Analysis in Small Bowel Adenocarcinomas with Verified Mutational Landscape and Predisposing Conditions

Background: Small bowel adenocarcinoma (SBA) is a rare yet insidious cancer with poor survival. The abundance of tumour-infiltrating lymphocytes is associated with improved survival, but the role of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway in tumour escape is controversial. We evaluated immune cell infiltration, PD1/PD-L1 expression and their prognostic value in a series of SBAs with previously verified predisposing conditions and exome-wide somatic mutation characterization. Methods: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 were analysed from 94 SBAs. An immune cell score (ICS) was formed from the amount of the CD3 and CD8 positive lymphocytes from the tumour centre and invasive margin. The PD-L1 and PD-1 positive immune cells (ICs) and ICS were combined into a variable called Immunoprofile. Results: High ICS, PD-L1IC and PD-1, individually and combined as Immunoprofile, were prognostic for better patient outcome. Sixty-five (69%) SBAs expressed ≥1% positive PD-L1IC. A high tumour mutation burden was common (19%) and associated with immune markers. Immunoprofile, adjusted for TNM stage, mismatch repair status, tumour location, sex and age were independent prognostic markers for disease-specific and overall survival. Conclusions: Analysing tumoral immune contexture provides prognostic information in SBA. Combining ICS, PD-1 and PD-L1IC as Immunoprofile enhanced the prognostic performance

Prognostic significance of spatial and density analysis of T lymphocytes in colorectal cancer

Background Although high T cell density is a strong favourable prognostic factor in colorectal cancer, the significance of the spatial distribution of T cells is incompletely understood. We aimed to evaluate the prognostic significance of tumour cell-T cell co-localisation and T cell densities. Methods We analysed CD3 and CD8 immunohistochemistry in a study cohort of 983 colorectal cancer patients and a validation cohort (N = 246). Individual immune and tumour cells were identified to calculate T cell densities (to derive T cell density score) and G-cross function values, estimating the likelihood of tumour cells being co-located with T cells within 20 mu m radius (to derive T cell proximity score). Results High T cell proximity score associated with longer cancer-specific survival in both the study cohort [adjusted HR for high (vs. low) 0.33, 95% CI 0.20-0.52, P-trend < 0.0001] and the validation cohort [adjusted HR for high (vs. low) 0.15, 95% CI 0.05-0.45, P-trend < 0.0001] and its prognostic value was independent of T cell density score. Conclusions The spatial point pattern analysis of tumour cell-T cell co-localisation could provide detailed information on colorectal cancer prognosis, supporting the value of spatial measurement of T cell infiltrates as a novel, robust tumour-immune biomarker.Peer reviewe

Valuing the commons : an international study on the recreational benefits of the Baltic Sea

The Baltic Sea provides benefits to all of the nine nations along its coastline, with some 85 million people living within the catchment area. Achieving improvements in water quality requires international cooperation. The likelihood of effective cooperation is known to depend on the distribution across countries of the benefits and costs of actions needed to improve water quality. In this paper, we estimate the benefits associated with recreational use of the Baltic Sea in current environmental conditions using a travel cost approach, based on data from a large, standardized survey of households in each of the 9 Baltic Sea states. Both the probability of engaging in recreation (participation) and the number of visits people make are modeled. A large variation in the number of trips and the extent of participation is found, along with large differences in current annual economic benefits from Baltic Sea recreation. The total annual recreation benefits are close to 15 billion EUR. Under a water quality improvement scenario, the proportional increases in benefits range from 7 to 18% of the current annual benefits across countries. Depending on how the costs of actions are distributed, this could imply difficulties in achieving more international cooperation to achieve such improvements.PostprintPeer reviewe

Substantial fat mass loss reduces low-grade inflammation and induces positive alteration in cardiometabolic factors in normal-weight individuals

( )The accumulation of fat, especially in visceral sites, is a significant risk factor for several chronic diseases with altered cardiometabolic homeostasis. We studied how intensive long-term weight loss and subsequent weight regain affect physiological changes, by longitudinally interrogating the lipid metabolism and white blood cell transcriptomic markers in healthy, normal-weight individuals. The current study examined 42 healthy, young (age: 27.5 +/- 4.0 years), normal-weight (body mass index, BMI: 23.4 +/- 1.7 kg/m(2)) female athletes, of which 25 belong to the weight loss and regain group (diet group), and 17 to the control group. Participants were evaluated, and fasting blood samples were drawn at three time points: at baseline (PRE); at the end of the weight loss period (MID: 21.1 +/- 3.1 weeks after PRE); and at the end of the weight regain period (POST: 18.4 +/- 2.9 weeks after MID). Following the weight loss period, the diet group experienced a similar to 73% reduction (similar to 0.69 kg) in visceral fat mass (false discovery rate, FDR <2.0 x 10(-16)), accompanied by anti-atherogenic effects on transcriptomic markers, decreased low-grade inflammation (e.g., as alpha(1)-acid glycoprotein (FDR = 3.08 x 10(-13)) and hs-CRP (FDR = 2.44 x 10(-3))), and an increase in functionally important anti-atherogenic high-density lipoprotein -associated metabolites (FDR <0.05). This occurred even though these values were already at favorable levels in these participants, who follow a fitness-lifestyle compared to age- and BMI-matched females from the general population (n = 58). Following the weight regain period, most of the observed beneficial changes in visceral fat mass, and meta bolomic and transcriptomic profiles dissipated. Overall, the beneficial anti-atherogenic effects of weight loss can be observed even in previously healthy, normal-weight individuals.Peer reviewe

Hard Tissue Engineering

Peer reviewe

Genetic and Epigenetic Characteristics of Inflammatory Bowel Disease–Associated Colorectal Cancer

doi: 10.1053/j.gastro.2021.04.042Background & Aims Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct pathway of tumorigenesis compared to sporadic CRC (sCRC). Our aim was to comprehensively characterize IBD-associated tumorigenesis integrating multiple high-throughput approaches, and to compare the results with in-house data sets from sCRCs. Methods Whole-genome sequencing, single nucleotide polymorphism arrays, RNA sequencing, genome-wide methylation analysis, and immunohistochemistry were performed using fresh-frozen and formalin-fixed tissue samples of tumor and corresponding normal tissues from 31 patients with IBD-CRC. Results Transcriptome-based tumor subtyping revealed the complete absence of canonical epithelial tumor subtype associated with WNT signaling in IBD-CRCs, dominated instead by mesenchymal stroma-rich subtype. Negative WNT regulators AXIN2 and RNF43 were strongly down-regulated in IBD-CRCs and chromosomal gains at HNF4A, a negative regulator of WNT-induced epithelial–mesenchymal transition (EMT), were less frequent compared to sCRCs. Enrichment of hypomethylation at HNF4α binding sites was detected solely in sCRC genomes. PIGR and OSMR involved in mucosal immunity were dysregulated via epigenetic modifications in IBD-CRCs. Genome-wide analysis showed significant enrichment of noncoding mutations to 5′untranslated region of TP53 in IBD-CRCs. As reported previously, somatic mutations in APC and KRAS were less frequent in IBD-CRCs compared to sCRCs. Conclusions Distinct mechanisms of WNT pathway dysregulation skew IBD-CRCs toward mesenchymal tumor subtype, which may affect prognosis and treatment options. Increased OSMR signaling may favor the establishment of mesenchymal tumors in patients with IBD.BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct pathway of tumorigenesis compared to sporadic CRC (sCRC). Our aim was to comprehensively characterize IBD-associated tumorigenesis integrating multiple high-throughput approaches, and to compare the results with in-house data sets from sCRCs. METHODS: Whole-genome sequencing, single nucleotide polymorphism arrays, RNA sequencing, genome-wide methylation analysis, and immunohistochemistry were performed using fresh-frozen and formalin-fixed tissue samples of tumor and corresponding normal tissues from 31 patients with IBD-CRC. RESULTS: Transcriptome-based tumor subtyping revealed the complete absence of canonical epithelial tumor subtype associated with WNT signaling in IBD-CRCs, dominated instead by mesenchymal stroma-rich subtype. Negative WNT regulators AXIN2 and RNF43 were strongly down-regulated in IBD-CRCs and chromosomal gains at HNF4A, a negative regulator of WNTinduced epithelial-mesenchymal transition (EMT), were less frequent compared to sCRCs. Enrichment of hypomethylation at HNF4 alpha binding sites was detected solely in sCRC genomes. PIGR and OSMR involved in mucosal immunity were dysregulated via epigenetic modifications in IBD-CRCs. Genome-wide analysis showed significant enrichment of noncoding mutations to 50 untranslated region of TP53 in IBD-CRCs. As reported previously, somatic mutations in APC and KRAS were less frequent in IBD-CRCs compared to sCRCs. CONCLUSIONS: Distinct mechanisms of WNT pathway dysregulation skew IBD-CRCs toward mesenchymal tumor subtype, which may affect prognosis and treatment options. Increased OSMR signaling may favor the establishment of mesenchymal tumors in patients with IBD.Peer reviewe