Nitrogen (N) accumulation rates in peatland ecosystems indicate significant biological atmospheric N ₂ fixation associated with Sphagnum mosses. Here, we show that the linkage between methanotrophic ...carbon cycling and N ₂ fixation may constitute an important mechanism in the rapid accumulation of N during the primary succession of peatlands. In our experimental stable isotope enrichment study, previously overlooked methane-induced N ₂ fixation explained more than one-third of the new N input in the younger peatland stages, where the highest N ₂ fixation rates and highest methane oxidation activities co-occurred in the water-submerged moss vegetation.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Background and aims Nitrogen (N2) fixation by moss-associated bacteria is an important N source in boreal peatlands and forests. Here we studied whether moss species, water table fluctuations, ...methane (CH4) availability and diazotroph community structure would affect the rate of Sphagnum-associated N2 fixation. Methods Diazotrophy and methanotrophy were studied in parallel in a double labeling (15N2 and 13CH4) experiment in forest and fen habitats. The role of N2-fixing methanotrophs was further characterized by the phylogenetic analysis of nifH genes encoding for dinitrogenase reductase. Results N2 fixation rates were dependent on the moss species in a habitat level, but independent of the diazotroph community structure. Only 6 % of the nifH sequences were taxonomically assigned to cyanobacteria, while the majority (82 %) of genes were assigned to Alphaproteobacteria clustering with the nifH sequences of the order Rhizobiales, but without close matches to sequences of cultivated species. In the originally submerged fen mosses, water increased both N2 fixation and CH4 oxidation rates. However, such effect was not seen in forest mosses grown above the water table level. CH4 addition did not enhance N2 fixation. Conclusions N2 fixation associated to Sphagnum mosses was controlled by the moss species and the water environment. Although most of the observed nifH sequences were related to the order Rhizobiales, methanotrophs were not responsible for the N2 fixation.
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BFBNIB, DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
► N2 fixation in forest mosses was studied using acetylene reduction and 15N2 methods. ► The methods gave corresponding results with the conversion factor of 3.3. ► Moss-associated N2 fixation was ...higher in the northern samples with low N deposition. ► Methanotrophic activity associated with forest mosses was low.
Nitrogen deposition has decreased the plant-associated nitrogen (N2) fixation when measured using the indirect acetylene reduction assay (ARA). However, nitrogen deposition can also lead to changes in the diversity of moss symbionts, e.g. affect methanotrophic N2 fixation, which is not measured by ARA. To test this hypothesis we compared ARA with the direct stable isotope method (15N2 incorporation) and studied methanotrophy in two mosses, Hylocomium splendens and Pleurozium schreberi, collected from seven forest sites along a boreal latitudinal N deposition transect. We recognized that the two independent N2 fixation measures gave corresponding results with the conversion factor of 3.3, but the 15N2 method was more sensitive for finding a signal of low N2 fixation activity. Methane carbon fixation associated with mosses was under the detection limit (<2nmolCg−1h−1). N2 fixation rates were more pronounced in the mosses with higher C/N ratio, and in the green upper parts of the shoot than in the lower brownish parts. Sequencing of nifH genes revealed that dominating diazotrophs were affiliated to cyanobacterial genera Nostoc and Nodularia, but methanotrophic diazotrophs were not found in the nifH libraries. We conclude that the suppression of N2 fixation along the deposition gradient was consistent regardless of the measurement technique, and microbial community changes toward methanotrophic or otherwise acetylene-sensitive N2 fixation could not explain this trend.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Dead wood is initially a nitrogen (N) poor substrate, where the N content increases with decay, partly due to biological N2 fixation, but the drivers of the N accumulation are poorly known. We ...quantified the rate of N2 fixation in decaying Norway spruce logs of different decay stages and studied the potential regulators of the N2-fixation activity. The average rate for acetylene reduction in the decaying wood was 7.5 nmol ethylene g−1d−1, which corresponds to 52.9 μg N kg−1d−1. The number of nifH copies (g−1 dry matter) was higher at the later decay stages, but no correlation between the copy number and the in vitro N2 fixation rate was found. All recovered nifH sequences were assigned to the order Rhizobiales, and therein mostly (60%) to methane oxidizing genera. We confirm that nitrogen fixing methanotrophs are present in all the wood decay phases and suggest that their interaction between methane producing organisms in decaying wood should be further studied.
•N2 fixing bacteria are active in decaying wood.•The number of nifH copies was higher at later decay stages.•No correlation between nifH copy number and in vitro N2 fixation rate was found.•60% of the nifH sequences were assigned to methane oxidizing bacteria.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We conducted a genome-wide analysis to identify differentially methylated genes in atherosclerotic lesions.
DNA methylation at promoters, exons and introns was identified by massive parallel ...sequencing. Gene expression was analysed by microarrays, qPCR, immunohistochemistry and western blots.
Globally, hypomethylation of chromosomal DNA predominates in atherosclerotic plaques and two-thirds of genes showing over 2.5-fold differential in DNA methylation are up-regulated in comparison to healthy mammary arteries. The imprinted chromatin locus 14q32 was identified for the first time as an extensively hypomethylated area in atherosclerosis with highly induced expression of miR127, -136, -410, -431, -432, -433 and capillary formation-associated gene RTL1. The top 100 list of hypomethylated promoters exhibited over 1000-fold enrichment for miRNAs, many of which mapped to locus 14q32. Unexpectedly, also gene body hypermethylation was found to correlate with stimulated mRNA expression.
Significant changes in genomic methylation were identified in atherosclerotic lesions. The most prominent gene cluster activated via hypomethylation was detected at imprinted chromosomal locus 14q32 with several clustered miRNAs that were up-regulated. These results suggest that epigenetic changes are involved in atherogenesis and may offer new potential therapeutic targets for vascular diseases.
In Parkinson's disease, brain dopamine neurons degenerate most prominently in the substantia nigra. Neurotrophic factors promote survival, differentiation and maintenance of neurons in developing and ...adult vertebrate nervous system. The most potent neurotrophic factor for dopamine neurons described so far is the glial-cell-line-derived neurotrophic factor (GDNF). Here we have identified a conserved dopamine neurotrophic factor (CDNF) as a trophic factor for dopamine neurons. CDNF, together with its previously described vertebrate and invertebrate homologue the mesencephalic-astrocyte-derived neurotrophic factor, is a secreted protein with eight conserved cysteine residues, predicting a unique protein fold and defining a new, evolutionarily conserved protein family. CDNF (Armetl1) is expressed in several tissues of mouse and human, including the mouse embryonic and postnatal brain. In vivo, CDNF prevented the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons in a rat experimental model of Parkinson's disease. A single injection of CDNF before 6-OHDA delivery into the striatum significantly reduced amphetamine-induced ipsilateral turning behaviour and almost completely rescued dopaminergic tyrosine-hydroxylase-positive cells in the substantia nigra. When administered four weeks after 6-OHDA, intrastriatal injection of CDNF was able to restore the dopaminergic function and prevent the degeneration of dopaminergic neurons in substantia nigra. Thus, CDNF was at least as efficient as GDNF in both experimental settings. Our results suggest that CDNF might be beneficial for the treatment of Parkinson's disease.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The mismatch negativity (MMN) component of event-related potentials (ERPs), a measure of passive change detection, is suggested to develop early in comparison to other ERP components, and an MMN-like ...response has been measured even from preterm infants. The MMN response in adults is negative in polarity at about 150–200 ms. However, the response measured in a typical MMN paradigm can also be markedly different in newborns, even opposite in polarity. This has been suggested to be related to maturational factors. To verify that suggestion, we measured ERPs of 21 newborns during quiet sleep to rarely occurring deviant tones of 1100 Hz (probability 12%) embedded among repeated standard tones of 1000 Hz in an oddball sequence. Gestational age (GA) and two cardiac measures, vagal tone (V) and heart period (HP), were used as measures of maturation. GA and HP explained between 36% and 42% of the total variance of the individual ERP peak amplitude (the largest deflection of the difference wave at a time window of 150–375 ms) at different scalp locations. In the discriminant function analyses, GA and HP as classifying variables differentiated infants in whom the peak of the difference wave had positive polarity from those with a negative polarity at an accuracy level ranging from 72% to 91%. These results demonstrate that during quiet sleep, maturational factors explain a significant portion of the ERP difference wave amplitude in terms of its polarity, indicating that the more mature the ERPs are, the more positive the amplitude. The present study suggests that maturational effects should be taken into account in ERP measurements using MMN paradigms with young infants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Inhibition of Autotaxin (ATX) is a potential treatment strategy for several diseases, including tumors with elevated ATX-lysophosphatidic acid (LPA) signaling. Combining structure-based virtual ...screening together with hen egg-white Autotaxin (ewATX) activity assays enabled the discovery of novel small-molecule ATX inhibitors with a 2,4-dihydropyrano2,3-cpyrazole scaffold. These compounds are suggested to bind to the lipophilic pocket, leaving the active site unrestrained. Our most potent compound, (S)-6-amino-4-(3,4-dichlorophenyl)-3-(4-(4-fluorobenzyl)oxyphenyl)-2,4-dihydropyrano2,3-cpyrazole-5-carbonitrile (S)-25, inhibited human ATX (hATX) with an IC50-value of 134nM. It also blocked ATX-evoked but not LPA-mediated A2058 melanoma cell migration. Noteworthy, molecular modeling correctly predicted the biologically active enantiomer of 2,4-dihydropyrano2,3-cpyrazoles, as verified by compound crystallization and activity assays. Our study established the ewATX activity assay as a valid and affordable tool in ATX inhibitor discovery. Overall, our study offers novel insights and approaches into design of novel ATX inhibitors targeting the hydrophobic pocket instead of the active site.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background
The senses of smell and taste can be adversely affected by both tumour- and treatment-related factors amongst head and neck cancer patients. The consequences may negatively impact ...nutritional status as well as quality of life in this patient population.
Patients and methods
This prospective longitudinal follow-up study is consisted of 44 patients treated for oral cavity, oropharyngeal or hypopharyngeal cancer with tumour resection and microvascular free tissue transfer reconstruction at the Helsinki University Hospital, Helsinki, Finland. Thirty-nine (89%) of them also received radiotherapy. The senses of smell (odour detection, identification and threshold test) and taste (electrogustometry) and quality of life (UW-QOL) were evaluated preoperatively, and at 6 weeks, 3 months, 6 months and 12 months, postoperatively.
Results
There were higher scores in the odour detection values in the 6-week and 3-month tests compared with preoperative values for the tumour side. Other detection scores did not differ statistically from the preoperative values neither in the tumour nor the contralateral side. However, in the odour identification test, all posttreatment values were statistically significantly higher than pretreatment ones. In the olfactory threshold test, no statistically significant differences were found between pre- and posttreatment values. Electrogustometry values for the taste on the tumour side were statistically significantly impaired at 6 weeks (
p
< 0.05) and at 3 months (
p
< 0.01) compared with the pretreatment results. They were also impaired at 6 months and at 12 months, although the differences were not statistically significant. The quality of life was impaired after treatment in this patient series. However, the correlation between quality of life and sense of taste was found only at one time point (3 months) and only with contralateral side measurements.
Conclusions
We conclude that in oral and pharyngeal cancer patients the postoperative taste problems are related to the impairment on the taste sensation in the tongue but not with the sense of smell. Moreover, the impairment in the quality of life is not clearly related to the impaired sense of taste.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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