Hepatologia erikoisalana : hepatologian koulutusta lisättävä - myös Suomessa

Teema : hepatologi

The solution structure of the amino-terminal domain of human DNA polymerase ε subunit B is homologous to C-domains of AAA+ proteins

DNA polymerases α, δ and ε are large multisubunit complexes that replicate the bulk of the DNA in the eukaryotic cell. In addition to the homologous catalytic subunits, these enzymes possess structurally related B subunits, characterized by a carboxyterminal calcineurin-like and an aminoproximal oligonucleotide/oligosaccharide binding-fold domain. The B subunits also share homology with the exonuclease subunit of archaeal DNA polymerases D. Here, we describe a novel domain specific to the N-terminus of the B subunit of eukaryotic DNA polymerases ε. The N-terminal domain of human DNA polymerases ε (Dpoe2NT) expressed in Escherichia coli was characterized. Circular dichroism studies demonstrated that Dpoe2NT forms a stable, predominantly α-helical structure. The solution structure of Dpoe2NT revealed a domain that consists of a left-handed superhelical bundle. Four helices are arranged in two hairpins and the connecting loops contain short β-strand segments that form a short parallel sheet. DALI searches demonstrated a striking structural similarity of the Dpoe2NT with the α-helical subdomains of ATPase associated with various cellular activity (AAA+) proteins (the C-domain). Like C-domains, Dpoe2NT is rich in charged amino acids. The biased distribution of the charged residues is reflected by a polarization and a considerable dipole moment across the Dpoe2NT. Dpoe2NT represents the first C-domain fold not associated with an AAA+ protein

Temporal trends in Finnish agricultural soils: A comparative analysis of national and LUCAS soil monitoring datasets

Finnish agricultural soil conditions are regularly monitored both through national and European Union (EU)-wide LUCAS Soil sampling. In this study, we compare temporal trends and variability in organic carbon content (OC), pH, phosphorus (P) and potassium (K) in 2009–2018 across the two datasets. The national monitoring programme encompasses more monitoring plots (620 vs. 134 in 2018), while LUCAS sampling is repeated more frequently and in addition to 2009 and 2018, it also includes data from 2015. The temporal variability in all examined indicators was substantially higher in the LUCAS dataset compared to the national monitoring data. In mineral soils, Spearman's rank correlation coefficient between element contents measured in 2009 and 2018 ranged between 0.82 and 0.94 in the national dataset, and between 0.52 and 0.67 in the LUCAS dataset. The results for organic soils mirrored those of mineral soils. The higher variability in the LUCAS dataset may be attributed to less precise geolocation of sampling plots and/or variations in the sampling protocol such as greater sampling depth and the use of a spade instead of a core auger. The greater temporal variability, coupled with a smaller number of sampling plots in the LUCAS dataset, resulted in lower statistical power making the detection of trends with a realistic magnitude more challenging. Further, in LUCAS data, the confidence intervals of trends were of the same magnitude, regardless of whether the data from the year 2015 was included or not. The national dataset was found to be sufficient for detecting nationwide trends in element contents. Our results indicate that refining sampling protocols and improving the location accuracy of sampling plots are more cost-effective approaches to enhance the precision of temporal trend estimation than increasing the number of sampling plots

Soil organic carbon and clay content as deciding factors for net nitrogen mineralization and cereal yields in boreal mineral soils

To achieve appropriate yield levels, inherent nitrogen (N) supply and biological N fixation are often complemented by fertilization. To avoid economic losses and negative environmental impacts due to over-application of N fertilizer, estimation of the inherent N supply is critical. We aimed to identify the roles of soil texture and organic matter in N mineralization and yield levels attained in cereal cultivation with or without N fertilization in boreal mineral soils. First, the net N mineralization and soil respiration were measured by laboratory incubation with soil samples varying in clay and organic carbon (C) contents. Secondly, to estimate the inherent soil N supply under field conditions, both unfertilized and fertilized cereal yields were measured in fields on clay soils (clay 30-78%) and coarse-textured soils (clay 0-28%). In clay soils (C 2.5-9.0%), both the net N mineralization and the cereal yields (without and with fertilization) decreased with increasing clay/C ratio. Moreover, in soils with high clay/C ratio, the agronomic N use efficiency (additional yield per kg of fertilizer N) varied considerably, indicating the presence of growth limitations other than N. In coarse-textured soils, the yield increase attained by fertilization increased with increasing organic C. Our results indicate that for clay soils in a cool and humid climate, the higher the clay content, the more organic C is needed to produce reasonable yields and to ensure efficient use of added nutrients without high N losses to the environment. For coarse soils having a rather high mean organic C of 2.3%, the organic C appeared to improve agronomic N use efficiency. For farmers, simple indicators such as the clay/C ratio or the use of non-N-fertilized control plots may be useful for site-specific adjustment of the rates of N fertilization. Highlights We aimed to identify simple indicators of inherent soil N supply applicable at the farm level. In clay soils, the net N mineralization was found to correlate negatively with the clay/C ratio. In coarse-textured soils, agronomic N use efficiency improved with increasing soil organic C. Clay soils with high clay/C ratio are at risk of low yield levels.Peer reviewe

Prediction of renal outcome in Henoch-Schonlein nephritis based on biopsy findings

Background In Henoch-Schonlein nephritis (HSN), a risk factor for unfavorable outcome is prolonged proteinuria, but the value of renal biopsies in prognosis assessment is debatable. Methods We evaluated serial renal biopsies from 26 HSN patients. Follow-up biopsy occurred at median 2.1 years after diagnostic biopsy. Patients formed two groups at the follow-up biopsy: patients without proteinuria (group I; n = 11) and with proteinuria (group II; n = 15). Biopsies underwent evaluation according to three classifications: International Study of Kidney Disease in Children (ISKDC), Oxford (MEST-C), and semiquantitative classification (SQC) including an activity and chronicity score. Analysis also included expression of pro-fibrotic (alpha-smooth muscle actin and vimentin) and inflammatory (P-selectin glycoprotein ligand-1) molecules in the diagnostic biopsy specimens. Definition of unfavorable outcome was active renal disease or reduced renal function at last follow-up. Results Between the biopsies, SQC chronicity score increased in 22 (85%) patients, whereas activity score and ISKDC grade decreased in 21 (81%) and 17 (65%), respectively. Of the MEST-C parameters, endocapillary proliferation (from 83 to 13%; p <0.001) and crescents (from 63 to 25%; p = 0.022) showed significant reduction, and segmental glomerulosclerosis (from 38 to 79%; p = 0.006) significant increment. These changes occurred similarly in groups I and II. Expression of the pro-fibrotic and inflammatory molecules showed no clinically significant differences between groups I and II. None in group I and five (33%) patients in group II had unfavorable outcome (p = 0.053). Conclusions Our results suggest that follow-up biopsies provide limited additional information to clinical symptoms in HSN outcome prediction.Peer reviewe

FOXP3(+) T cells are present in kidney biopsy samples in children with tubulointerstitial nephritis and uveitis syndrome

Tubulointerstitial nephritis (TIN) is an inflammatory disease of unknown pathogenesis. To evaluate a possible role of regulatory T cells (Tregs) in the pathophysiology of TIN with (TINU) and without uveitis, we investigated the presence and quantity of FOXP3(+) T regulatory lymphocytes in diagnostic kidney biopsies from pediatric patients. A total of 33 patients (14 TIN and 19 TINU) were enrolled. The quantity of CD4(+), FOXP3(+) and double-positive T cells in formalin-fixed kidney biopsies was determined using double label immunohistochemistry with anti-human CD4 and FOXP3 antibodies. FOXP3 staining was successful in all 33 patients. In patients with chronic uveitis, the density of FOXP3(+) cells was significantly lower (p = 0.046) than in TIN patients without uveitis or with uveitis lasting <3 months. CD4(+) staining was successful in 23 patients. The density of all lymphocytes (CD4(+), CD4(+)FOXP3(+) and FOXP3(+) cells) was significantly lower (p = 0.023) in patients with chronic uveitis than in other patients. FOXP3(+) T cells are present in kidney biopsy samples from TIN and TINU patients. In patients with chronic uveitis, the density of FOXP3(+) T cells is significantly lower than in other patients, suggesting a different pathomechanism for these clinical conditions.Peer reviewe

The ISKDC classification and a new semiquantitative classification for predicting outcomes of Henoch-Schonlein purpura nephritis

Histological findings from primary kidney biopsies were correlated with patient outcomes in a national cohort of paediatric Henoch-Schonlein nephritis (HSN) patients. Primary kidney biopsies from 53 HSN patients were re-evaluated using the ISKDC (International Study of Kidney Disease in Children) classification and a modified semiquantitative classification (SQC) that scores renal findings and also takes into account activity, chronicity and tubulointerstitial indices. The ISKDC and SQC classifications were evaluated comparatively in four outcome groups: no signs of renal disease (outcome A, n = 27), minor urinary abnormalities (outcome B, n = 18), active renal disease (outcome C, n = 3) and renal insufficiency, end-stage renal disease or succumbed due to HSN (outcome D, n = 5). For the receiver operating characteristic and logistic regression analyses, outcomes A and B were considered to be favourable and outcomes C and D to be unfavourable. The median follow-up time was 7.3 years. The patients with an unfavourable outcome (C and D), considered together due to low patient numbers, had significantly higher total biopsy SQC scores and activity indices than those who had a favourable one (groups A and B). The chronicity and tubulointerstitial indices differed significantly only between group C + D and group A. The difference in areas under the curve between the total biopsy SQC scores and ISKDC findings was 0.15 [p = 0.04, normal-based 95% confidence interval (CI) 0.007-0.29, bias-controlled 95% CI -0.004 to 0.28]. Our results suggest that the modified SQC is more sensitive than ISKDC classification for predicting the outcome in HSN cases.Peer reviewe

Laboratorioiden välinen pätevyyskoe 11/2016 - Haihtuvat orgaaniset yhdisteet vedestä ja maasta

Proftest SYKE järjesti marraskuussa 2016 pätevyyskokeen laboratorioille, jotka määrittävät haihtuvia orgaanisia yhdisteitä (VOC) vedestä ja maasta. Osallistujille toimitettiin synteettinen näyte, talous- ja pintavesinäytteet sekä maanäyte. Pätevyyskokeeseen osallistui 10 laboratoriota. Vertailuarvona käytettiin testisuureesta ja näytteestä riippuen laskennallista arvoa tai osallistujien tulosten keskiarvoa. Pätevyyden arvioinnissa käytettiin z-arvoa ja sitä laskettaessa tuloksille sallittiin näytteestä ja testisuureesta riippuen 15–35 %:n poikkeama vertailuarvosta. Tulosaineistossa oli hyväksyttäviä tuloksia 81 %. Testisuureelle ETBE ei näytteen M4V osalta voitu tulosten vähäisen määrän vuoksi laskea z-arvoja, vaan tuloksia on arvioitu D%- ja En-arvoilla. Kiitos pätevyyskokeen osallistujille

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