Microbiological tests and measurements in the assessment of harmful substances and pollution

New chemicals are produced in increasing numbers. In Finland every year about 28 000 different products are manufactured or imported which can be classified as harmful. These products contain about 5000 different harmful substances. We also receive harmful compounds in airborne emissions. Substances are further transformed in industrial processes, in waste management and in the environment by human activities and natural processes. However, only rather limited monitoring data is available about the environmental concentrations of these compounds (concerning about 20–40 substances). The environmental risks of harmful substances can be recognized, assessed and managed by : 1) measuring concentrations in the environment, 2) testing the effects on biota in toxicity tests and 3) monitoring ecosystem changes in the environment. Microbes have a key role in the environment as degraders in the carbon and nutrient cycles. They also have the capability to transform and degrade many harmful man-made substances. Microbes have a strong effect on the exposure of other biota to chemical substances. Hence they can be regarded as primary targets for harmful effects of chemicals or active transformers of chemicals in the environment.The objective of this study was to evaluate the usefulness and applicability of microbial toxicity tests, biodegradation tests and microbial biomass and activity measurements in the environment for the environmental hazard identification and risk assessment of chemicals, effluents and contaminated soils. The study considers both aquatic and soil environments. The effects of modern pulp mill bleaching effluents on biota were assessed by a set of different biotests and by chemical analysis. The effluents and their long term effects on aquatic microbial processes were also studied in outdoor mesocosms. In one part the biodegradation kinetics of carbon-14-labeled model compounds in standard tests and in environmental conditions were measured and compared. The effects of several pesticides on soil microbes were tested and assessed in laboratory tests and in field trials. The applicability of microbial toxicity tests in the assessment of soil pollution and bioremediation processes was also studied in comparison with chemical analysis. The results of the study can support the development and selection of test methods for environmental risk management and regulatory decisions

Historiankirjoitus – Kansakunnan kompassi vai politiikan tuuliviiri

Historian loputon moninaisuus on hämmentänyt niin suurta lukevaa yleisöä kuin tutkijoitakin. Jo historian puristaminen määritelmäksi on osoittautunut niin hankalaksi, että eräät tiedemiehet ovat epäilleet koko yrityksen mielekkyyttä. Lukuisia määritysyrityksiä on vaikeuksista huolimatta kuitenkin tehty. Useimmissa niissä korostuu historian kenties tärkein ulottuvuus, ihmisen halu ymmärtää itseään, yhteisöään ja yhteiskuntaansa pitkän ajallisen perspektiivin tarjoamasta näkökulmasta. Historiaa onkin luonnehdittu milloin inhimillisen toiminnan muodoksi, jossa kulttuuri tekee tiliä menneisyydestään, milloin kansakunnan kokemusvarastoksi, usein ihmiskunnan järjestäytyneeksi muistiksi, joskus peiliksi josta kansa tunnistaa itsensä osana esi-isiensä perintöä

Leaching resulting from land application of sewage sludge and slurry

Jätevesilietteestä ja lietelannasta aiheutuva huuhtoutumine

Does breast carcinoma belong to the Lynch syndrome tumor spectrum? - Somatic mutational profiles vs. ovarian and colorectal carcinomas

: ; ; ; ;Inherited DNA mismatch repair (MMR) defects cause predisposition to colorectal, endometrial, ovarian, and other cancers occurring in Lynch syndrome (LS). It is unsettled whether breast carcinoma belongs to the LS tumor spectrum. We approached this question through somatic mutational analysis of breast carcinomas from LS families, using established LS-spectrum tumors for comparison. Somatic mutational profiles of 578 cancer-relevant genes were determined for LS-breast cancer (LS-BC, n = 20), non-carrier breast cancer (NC-BC, n = 10), LS-ovarian cancer (LS-OC, n = 16), and LS-colorectal cancer (LS-CRC, n = 18) from the National LS Registry of Finland. Microsatellite and MMR protein analysis stratified LS-BCs into MMR-deficient (dMMR, n = 11) and MMR-proficient (pMMR, n = 9) subgroups. All NC-BCs were pMMR and all LS-OCs and LS-CRCs dMMR. All but one dMMR LS-BCs were hypermutated (> 10 non-synonymous mutations/Mb; average 174/Mb per tumor) and the frequency of MMR-deficiency-associated signatures 6, 20, and 26 was comparable to that in LS-OC and LS-CRC. LS-BCs that were pMMR resembled NC-BCs with respect to somatic mutational loads (4/9, 44%, hypermutated with average mutation count 33/Mb vs. 3/10, 30%, hypermutated with average 88 mutations/Mb), whereas mutational signatures shared features of dMMR LS-BC, LS-OC, and LS-CRC. Epigenetic regulatory genes were significantly enriched as mutational targets in LS-BC, LS-OC, and LS-CRC. Many top mutant genes of our LS-BCs have previously been identified as drivers of unselected breast carcinomas. In conclusion, somatic mutational signatures suggest that conventional MMR status of tumor tissues is likely to underestimate the significance of the predisposing MMR defects as contributors to breast tumorigenesis in LS.Peer reviewe

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

Epidemiological, clinical and molecular characterization of Lynch-like syndrome : A population-based study

Colorectal carcinomas that are mismatch repair (MMR)-deficient in the absence of MLH1 promoter methylation or germline mutations represent Lynch-like syndrome (LLS). Double somatic events inactivating MMR genes are involved in the etiology of LLS tumors. Our purpose was to define the clinical and broader molecular hallmarks of LLS tumors and the population incidence of LLS, which remain poorly characterized. We investigated 762 consecutive colorectal carcinomas operated in Central Finland in 2000-2010. LLS cases were identified by a stepwise protocol based on MMR protein expression, MLH1 methylation and MMR gene mutation status. LLS tumors were profiled for CpG Island Methylator Phenotype (CIMP) and somatic mutations in 578 cancer-relevant genes. Among 107 MMR-deficient tumors, 81 (76%) were attributable to MLH1 promoter methylation and 9 (8%) to germline mutations (Lynch syndrome, LS), leaving 14 LLS cases (13%) (3 remained unclassified). LLS carcinomas were diagnosed at a mean age of 65 years (vs. 44 years in LS, p <0.001), had a proximal to distal ratio of 1:1, and all were BRAF V600E-negative. Two somatic events in MMR genes were identifiable in 11 tumors (79%). As novel findings, the tumors contained an average of 31 nonsynonymous somatic mutations/Mb and 13/14 were CIMP-positive. In conclusion, we establish the epidemiological, clinical and molecular characteristics of LLS in a population-based study design. Significantly more frequent CIMP-positivity and lower rates of somatic mutations make a distinction to LS. The absence of BRAF V600E mutation separates LLS colorectal carcinomas from MLH1-methylated colorectal carcinomas with CIMP-positive phenotype.Peer reviewe