Genome-wide methylation profiling identifies hypermethylated biomarkers in high-grade cervical intraepithelial neoplasia

Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions was studied using genome-wide DNA methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methylated DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium. Hypermethylated differentially methylated regions (DMRs) were identified. Validation of nine selected DMRs using BSP and MSP in cervical tissue revealed methylation in 63.2–94.7% high-grade CIN and in 59.3–100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was conducted exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples. Clinical validation of both markers in cervical scrapings from patients with an abnormal cervical smear confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion and that ROC analysis was discriminative. These markers represent the COL25A1 and KATNAL2 and their observed increased methylation upon progression could intimate the regulatory role in carcinogenesis. In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and are candidate biomarkers for early detection.     

Litter quality in a north European transect versus carbon storage potential

Newly shed foliar plant litter often has a decomposition rate of ca 0.1–0.2% day^–1, which decreases greatly with time and may reach 0.0001 to 0.00001% day^–1 or lower in litter material in the last stages of decay. The decrease in decomposability (substrate quality) varies among species and is complex, involving both direct chemical changes in the substrate itself and the succession in microorganisms able to compete for substrate with a given chemical composition. In late stages, the decomposition appears very little affected by climate, suggesting that climate change will have little effect on late-stages decomposition rates. Here, we apply a model for the late stages of litter decomposition to address the question of climate-change effects on soil-C storage. Decomposition of litter turning into soil organic matter (SOM) is determined by the degradation rate of lignin. In the last phases of decay, raised N concentrations have a rate-retarding effect on lignin degradation and thus on the decomposition of far-decomposed litter and litter in near-humus stages. The retardation of the decomposition rate in late stages may be so strong that decomposition reaches a limit value at which total mass losses virtually stop. At such a stage the remaining litter would be close to that of stabilized SOM. The estimated limit values for different species range from about 45 to 100% decomposition indicating that between 0 and 55% should either be stabilized or decompose extremely slowly. For no less than 106 long-term studies on litter decomposition, encompassing 21 litter types, limit values were significantly and negatively related to N concentration, meaning that the higher the N concentration in the newly shed litter (the lower the C/N ratio) the more litter was left when it reached its limit value. Trees growing under warmer and wetter climates (higher actual evapotranspiration, AET) tend to shed foliar litter more rich in N than those growing under colder and drier climates. A change in climate resulting in higher AET would thus mean that within species, e.g., Scots pine, a higher N level in the foliar litter may result. Further, within the boreal system deciduous species appear to have foliar litter richer in N than have conifers and within the conifers group, Norway spruce has needle litter more rich in N than, e.g., Scots pine. Thus, a change of species (e.g., by planting) from pine to spruce or from spruce to a deciduous species such as birch may result in a higher N level in the litter fall at a given site. In both cases the result would be a lower limit value for decomposition. The paper presents an hypothesis, largely based on available data that a change in climate of 4° higher annual average temperature and 40% higher precipitation in the Baltic basin would result in higher N levels in litter, lower decomposition and thus a considerable increase in humus accumulation.     

A new semi-automated instrument to improve the fine needle aspiration procedure during breast lesion cell sampling

A large and increasing number of women in the western world will at some point during their life be investigated morphologically for some type of breast lesion. Fine Needle Aspiration (FNA) is one morphological method which is considered to be the fastest, cheapest and the most patient-friendly approach. However, the frequency of conclusive samples using this method varies and is often too low, especially when performed by unexperienced operators. In this study we have developed and tested a new semi-automated instrument (“CytoTest”) designed for FNA which is intended to improve the efficacy of the technique by increasing the percentage of conclusive samples. A total of 443 consecutive aspiration procedures on palpable breast lesions were performed to compare this new “CytoTest” equipment with the standard protocol using the same type of needles. We conclude that by increasing the extent and frequency of the reciprocatory motions used by an experienced sampling operator as well as enhancing the ejection pressure, the cellular yield can be increased almost three folded compared to the standard protocol. For cases with high amounts of non-diagnostic material (such as blood or cystic fluid) which were discarded, up to four times more sample could be obtained. Furthermore, the frequency of sparse samples under 1 mg was halved with use of the “CytoTest”.     

Effects of antalarmin,a CRF receptor 1 antagonist,on fright reaction and endocrine stress response in crucian carp (<Emphasis Type="Italic">Carassius carassius</Emphasis>)

The corticotrophin-releasing factor (CRF) receptors show striking homogeneity throughout the vertebrate subphylum. In mammals, the CRF(1) receptor (CRFR(1)) plays an important role in mediating behavioral and endocrine responses to fear and stress. The specific roles of this receptor subtype in fear and stress reactions in non-mammalian vertebrates are largely unknown. Crucian carp displays the olfactory-mediated fright reaction, a stereotypic behavioral response to waterborne cues from damaged skin of conspecifics. This reaction shows several similarities to basic components of avoidance behavior in mammals. In the present study, we applied the non-peptide CRFR(1) antagonist, antalarmin, to crucian carp 1 h before exposure to conspecific skin extract. This treatment resulted in a suppression of the fright reaction. After skin extract exposure, antalarmin treatment also lead to lower plasma cortisol values, as compared to vehicle treatment. This suppression of the behavioral fright reaction and the stress induced rise in plasma cortisol in crucian carp suggests that the functions of the CRFR(1) are conserved by evolution.     

Physiologische Untersuchungen über die Eireifung bei Pomatoceros triqueter L.

Ohne ZusammenfassungDie Untersuchungen wurden an der Zoologischen Station Kristineberg, Schweden, ausgeführt. Es ist mir eine angenehme Pflicht, dem Direktor, Herrn ProfessorHjalmar Théel, und dem Vorstand, Herrn Dr.Hjalmar Östergren, meinen besten Dank auszusprechen. Schließlich richte ich den herzlichsten Dank an Herrn Dr.John Runnström, Stockholm, der mir die Idee der Untersuchung gegeben und mit größtem Interesse und größter Freundlichkeit meine Arbeit geleitet hat.     

A revision of Hieracium (Asteraceae) in Norrbotten,northeastern‐most Sweden,revealed seven new species

The large quantity of material of Hieracium sectt. Hieracium, Vulgata, Bifida and Oreadea collected during the recently completed floristic inventory of the northeastern most Swedish province of Norrbotten has been revised. The number of species known from this previously badly under‐collected province hereby increased from 27 to 64, and seven species new to science were revealed. A diagnostic key to all 64 species is provided and H. alces T. Tyler, H. hystrix T. Tyler, H. larsii‐levii T. Tyler, H. pseudopsepharum T. Tyler, H. stenbergii T. Tyler, H. taedum T. Tyler and H. vexillatum T. Tyler are described anew.