The molecular biology of hypertensive congenital adrenal hyperplasia

The purpose of this project was to identify the molecular basis of hypertensive congenital adrenal hyperplasia in patients with two forms of the disease; steroid 17α-hydroxylase/17,20 lyase (CYP17) and 11β-hydroxylase (CYP11B1) deficiencies. These enzyme defects account for approximately 1% and 5% of recorded cases of congenital adrenal hyperplasia respectively. CYP17 is encoded by a single gene, CYP17 on chromosome 10. The CYP11B1 gene is located on chromosome 8q22, in tandem with the aldosterone synthase gene, CYP11B2, with which it shares 93% base sequence homology. The hypothesis was proposed that the higher incidence of CYP11B1 deficiency is the result of non-homologous recombination and gene conversion between the duplicated CYP11B genes. Two mutation screening methods were employed and evaluated. The first method involved construction of a genomic DNA library in bacteriophage lambda, isolation of fragments of CYP17 and subsequent sequencing by manual dideoxy chain termination to locate mutations in DNA from a single individual with 17α- hydroxylase deficiency. The second procedure used the polymerase chain reaction (PCR) and single strand conformation polymorphism analysis (SSCP) to screen DNA from several 11β-hydroxylase deficient patients simultaneously and proved to be a much faster and more successful approach to screening for mutations. A single point mutation was found on each allele of the CYP17 gene. In contrast point mutations, small deletions, small duplications and gene conversion events were found in the CYP11B genes, often with several mutations present in each patient. Deletion and duplication events occurred where there were direct repeats of base sequence. Pathological mutations in CYP11B1 were shown not to arise directly from gene conversion or non-homologous recombination in the subjects studied. Other factors, such as differences in the degree of DNA methylation and selection acting strongly against mutation within CYP17, may account for the higher rate of mutation at the CYP11B1 locus as compared to that of CYP17

Skeletal muscle as an experimental model of choice to study tissue aging and rejuvenation.

Skeletal muscle is among the most age-sensitive tissues in mammal organisms. Significant changes in its resident stem cells (i.e., satellite cells, SCs), differentiated cells (i.e., myofibers), and extracellular matrix cause a decline in tissue homeostasis, function, and regenerative capacity. Based on the conservation of aging across tissues and taking advantage of the relatively well-characterization of the myofibers and associated SCs, skeletal muscle emerged as an experimental system to study the decline in function and maintenance of old tissues and to explore rejuvenation strategies. In this review, we summarize the approaches for understanding the aging process and for assaying the success of rejuvenation that use skeletal muscle as the experimental system of choice. We further discuss (and exemplify with studies of skeletal muscle) how conflicting results might be due to variations in the techniques of stem cell isolation, differences in the assays of functional rejuvenation, or deciding on the numbers of replicates and experimental cohorts

Auswirkungen des langfristigen ökologischen Landbaus auf bodenbürtige Treibhausgasemissionen

Despite the increase in organic cropland, knowledge on the impact of organic farming on soil-derived nitrous oxide (N2O) and methane (CH4) emissions is rather limited. To improve the knowledge base, N2O and CH4 fluxes were investigated in a 571 day lasting cropping sequence in the “DOK” field trial. Two organic and two non-organic farming systems and an unfertilized control were chosen. For the whole monitoring, the two organic systems combined emitted 40% less N2O than the two non-organic ones cumulated on area-scale. Yield-scaled cumulated N2O emissions were nearly 10% lower for the organic systems combined, despite the yield gap of 27%. We found that besides N input, management induced soil quality properties drive differences in N2O emissions between farming systems as well. This supports the effort to invest in soil quality by ecological intensification not only to lower the environmental burden of agriculture but also to mitigate greenhouse gase

Determination of greenhouse gas sources and sinks in Swiss arable soils under organic and non-organic management

Agricultural practices contribute considerably to emissions of greenhouse gases (GHG). Knowledge on the impact of organic (ORG) compared to non-organic (NON-ORG) farming on soil-derived nitrous oxide (N2O) and methane (CH4) emissions is still limited. We conducted a literature search on measured soil GHG fluxes under ORG and NON-ORG from farming system comparisons and performed a meta-analysis. Based on 12 studies covering annual measurements, it appeared that area-scaled N2O emissions are with 14% significantly lower under ORG. However, yield-scaled N2O emissions are only 9% higher for ORG. Emissions from NON-ORG soils seemed to be influenced mainly by total N inputs, whereas for ORG other soil characteristics seemed to be more important because N2O from organic N fertilisers emits decoupled from the inputs. Furthermore, we observed a 12% higher CH4 uptake for arable soils under ORG

Potenziale des Ökolandbaus in Zeiten des Klimawandels - Geringere Lachgas-Emissionen vor allem auf biodynamischen Ackerböden

Anhand von Daten aus dem DOK Langzeit-Feldversuch in der Schweiz zeigen die Autoren, dass ökologische Anbausysteme im Mittel rund 40 % geringere flächenbezogene Emissionen aufweisen als konventionelle Systeme. Die geringsten Lachgas-Emissionen wurden im biodynamischen Anbausystem ermittelt, was möglicherweise auf die langjährige Kompostanwendung, die sich positiv auf den ph-Wert und auf das Bodenleben sowie die Bodenstruktur auswirkt, zurückzuführen ist

GREENHOUSE GAS FLUXES IN AGRICULTURAL SOILS UNDER ORGANIC AND NON-ORGANIC MANAGEMENT

Farming practices are known to exert strong control over the soils’ function to act as sources or sinks for greenhouse gases (GHG). This paper deals with the outcome of a recent meta-analysis based on the evaluation of 19 published long-term farming system comparisons. It provides a comprehensive data base regarding GHG fluxes from soils under organic and non-organic management. There is scientific evidence for lower nitrous oxide emissions from organically managed soils when scaled to the area. However, further data from farming system comparisons are required, particularly from long-term GHG measurements covering several cropping seasons or ideally entire crop rotations. This enables closing knowledge gaps concerning N fluxes and pools under organic management as well as the formation of the new soil ecosystem (soil quality) equilibrium after implementing organic practices. Substantial reductions of nitrous oxide emissions as well as enhancement of methane uptake can be reached by consequent application of “good agricultural practice” and simple adoptions of soil management, forming together a balanced set of GHG mitigation mechanisms. In addition we provide first GHG flux data from the well-known DOK farming system trial in Therwil/CH and the role of microbial communities driving soil functioning

SERS Microsensors for the Study of pH Regulation in Cystic Fibrosis Patient-Derived Airway Cultures

Acidification of the airway surface liquid in the respiratory system could play a role in the pathology of Cystic Fibrosis, but its low volume and proximity to the airway epithelium make it a challenging biological environment in which to noninvasively collect pH measurements. To address this challenge, we explored surface enhanced Raman scattering microsensors (SERS-MS), with a 4-mercaptobenzoic acid (MBA) pH reporter molecule, as pH sensors for the airway surface liquid of patient-derived in vitro models of the human airway. Using air–liquid interface (ALI) cultures to model the respiratory epithelium, we show that SERS-MS facilitates the optical measurement of trans-epithelial pH gradients between the airway surface liquid and the basolateral culture medium. SERS-MS also enabled the successful quantification of pH changes in the airway surface liquid following stimulation of the Cystic Fibrosis transmembrane conductance regulator (CFTR, the apical ion channel that is dysfunctional in Cystic Fibrosis airways). Finally, the influence of CFTR mutations on baseline airway surface liquid pH was explored by using SERS-MS to measure the pH in ALIs grown from Cystic Fibrosis and non-Cystic Fibrosis donors

Emission und Aufnahme von Lachgas und Methan durch Ackerböden in der Fruchtfolgesequenz Kunstwiese – Silomais unter konventioneller und biologischer Bewirtschaftung

Organic farming systems provide multiple environmental benefits. Concerning climate change they have a substantial mitigation potential. Skinner et al. (2014) evaluated with Meta-Analysis the global dataset on comparative field measurements of soil greenhouse gas (GHG) fluxes under organic and non-organic agricultural management that have been published by the end of 2012. They showed that for arable land-use under organic management compared to non-organic 1) the cumulated area-scaled N2O emissions are about 15 % lower, 2) yield-scaled N2O emissions are slightly higher and 3) CH4 uptake is higher. However, this database is thin and further field measurements covering whole crop rotations are needed to close knowledge gaps. Therefore soil GHG fluxes are measured since August 2012 in the DOK long-term experiment. Thereby the findings of the Meta-Analysis serve as hypotheses. The measurement results from a grass-clover - maize crop sequence confirm the hypotheses one and three. However hypothesis two was significantly rejected by the biodynamic system compared to the conventional system with farmyard manure

Kohlenstoffspeicherung und Treibhausgasflüsse in Böden unter biologischer und konventioneller Bewirtschaftung – Ergebnisse aus zwei globalen Meta-Analysen

Explorative literature searches followed by meta-analyses were conducted to identify differences in soil organic carbon (SOC) and soil-derived greenhouse gas emissions between organic and non-organic farming systems. Within a total of 74 studies we found significantly higher SOC concentrations, SOC stocks and C sequestration rates in organically managed soils compared to those under non-organic management. Meta-analysis of soil-derived GHG flux data from 19 studies revealed lower N2O emissions and higher CH4 uptake rates in soils under organic management when related to acreage. Due to lower yields in organic farming systems higher GHG emissions from these systems were obtained when the data was related to unit crop yield. The poor availability of farming system comparisons from developing countries, at present, renders the transfer of the obtained results to these extremely vulnerable environments difficult. However, the presented approach is open to regular updates once relevant data from these regions are published

Concomitant Carcinoma in situ in Cystectomy Specimens Is Not Associated with Clinical Outcomes after Surgery

Objective: The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients. Methods: The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC. Results: 1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups. Conclusions: We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making. Copyright (C) 2011 S. Karger AG, Base