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.     

Airway hyperresponsiveness to ultrasonically nebulized distilled water in subjects with tetraplegia.

The majority of otherwise healthy subjects with chronic cervical spinal cord injury (SCI) demonstrate airway hyperresponsiveness to aerosolized methacholine or histamine. The present study was performed to determine whether ultrasonically nebulized distilled water (UNDW) induces airway hyperresponsiveness and to further elucidate potential mechanisms in this population. Fifteen subjects with SCI, nine with tetraplegia (C4-7) and six with paraplegia (T9-L1), were initially exposed to UNDW for 30 s; spirometry was performed immediately and again 2 min after exposure. The challenge continued by progressively increasing exposure time until the forced expiratory volume in 1 s decreased 20% or more from baseline (PD20) or the maximal exposure time was reached. Five subjects responding to UNDW returned for a second challenge 30 min after inhalation of aerosolized ipratropium bromide (2.5 ml of a 0.6% solution). Eight of nine subjects with tetraplegia had significant bronchoconstrictor responses to UNDW (geometric mean PD20 = 7.76 +/- 7.67 ml), whereas none with paraplegia demonstrated a response (geometric mean PD20 = 24 ml). Five of the subjects with tetraplegia who initially responded to distilled water (geometric mean PD20 = 5.99 +/- 4.47 ml) were not responsive after pretreatment with ipratropium bromide (geometric mean PD20 = 24 ml). Findings that subjects with tetraplegia are hyperreactive to UNDW, a physicochemical agent, combined with previous observations of hyperreactivity to methacholine and histamine, suggest that overall airway hyperresponsiveness in these individuals is a nonspecific phenomenon similar to that observed in patients with asthma. The ability of ipratropium bromide to completely block UNDW-induced bronchoconstriction suggests that, in part, airway hyperresponsiveness in subjects with tetraplegia represents unopposed parasympathetic activity.     

Unterschiede im revier- und sexualverhalten endemisch-anatolischer zahnkarpfen (pisces,cyprinodontidae)

The endemic Anatolian cyprinodonts Aphanius chantrei, A. (Kosswigichtys) asquamatus, and A. anatoliae show definite interspecific differences in their territorial and sexual behaviour under laboratory conditions. Intraspecific differences were found in the nine populations of A. anatoliae investigated.A. chantrei and Kosswigichthys show almost the same territorial behaviour. In A. anatoliae territoriality is found in three populations; the remaining six populations show no territoriality.The sexual behaviour consists of visual display elements and of elements which enable the fish to keep close contact without actually touching each other. The sequence of elements can be variable. Only two populations of A. anatoliae have retained display elements; the remaining seven populations have lost all of them.A correlation is discussed between biotope conditions and sexual behaviour. Display and territorial behaviour may have become superfluous in extreme, sulphate-containing habitats, where a lack of flora has led to a lack of spawning sites. Under changing breeding conditions the newly evolved element with fish staying close together (male underneath the female) may have replaced the former display elements.     

Risikoberechnungen beim X-chromosomal rezessiven Erbgang

Using the example of Duchenne muscular dystrophy, risk calculations for X-linked recessive traits are performed using the Bayesian computation tableaus, demonstrating how to take even complex genetic models and their impact on the calculated risk into consideration.     

The cartilage-derived, C-type lectin (CLECSF1): structure of the gene and chromosomal location.

Cartilage is a tissue that is primarily extracellular matrix, the bulk of which consists of proteoglycan aggregates constrained within a collagen framework. Candidate components that organize the extracellular assembly of the matrix consist of collagens, proteoglycans and multimeric glycoproteins. We describe the human gene structure of a potential organizing factor, a cartilage-derived member of the C-type lectin superfamily (CLECSF1; C-type lectin superfamily) related to the serum protein, tetranectin. We show by Northern analysis that this protein is restricted to cartilage and locate the gene on chromosome 16q23. We have characterized 10.9 kb of sequence upstream of the first exon. Similarly to human tetranectin, there are three exons. The residues that are conserved between CLECSF1 and tetranectin suggest that the cartilage-derived protein forms a trimeric structure similar to that of tetranectin, with three N-terminal alpha-helical domains aggregating through hydrophobic faces. The globular, C-terminal domain that has been shown to bind carbohydrate in some members of the family and plasminogen in tetranectin, is likely to have a similar overall structure to that of tetranectin.     

The genus Alphitobius Stephens (Coleoptera,Tenebrionidae, Alphitobiini) in Africa and adjacent islands

All species of the genus Alphitobius Stephens, 1829 (Alphitobiini Reitter, 1917, subfamily Tenebrioninae Latreille, 1802) from Africa and adjacent islands are revised. New species: Alphitobius capitaneus sp. n. from Kenya. New synonyms: Cryptops ulomoides Solier, 1851, syn. n. of Alphitobius diaperinus (Panzer, 1796); Alphitobius rufus Ardoin, 1976, syn. n. of Alphitobius hobohmi Koch, 1953); Peltoides (Micropeltoides) crypticoides Pic, 1916, syn. n. of Peltoides (Micropeltoides) opacus (Gerstaecker, 1871), comb. n. Homonym: Alphitobius ulomoides Koch, 1953 = Alphitobius arnoldi nom. n. New combinations from Alphitobius: Ulomoides basilewskyi (Ardoin, 1969), comb. n.; Peltoides (Micropeltoides) opacus (Gerstaecker, 1871), comb. n. Figures of all examined species are added and a species key is compiled.