Palaeogenomics of Upper Palaeolithic to Neolithic European hunter-gatherers.

Modern humans have populated Europe for more than 45,000 years. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period. Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago.

Nuclear DNA from two early Neandertals reveals 80,000 years of genetic continuity in Europe.

Little is known about the population history of Neandertals over the hundreds of thousands of years of their existence. We retrieved nuclear genomic sequences from two Neandertals, one from Hohlenstein-Stadel Cave in Germany and the other from Scladina Cave in Belgium, who lived around 120,000 years ago. Despite the deeply divergent mitochondrial lineage present in the former individual, both Neandertals are genetically closer to later Neandertals from Europe than to a roughly contemporaneous individual from Siberia.

Deeply divergent archaic mitochondrial genome provides lower time boundary for African gene flow into Neanderthals.

Ancient DNA is revealing new insights into the genetic relationship between Pleistocene hominins and modern humans. Nuclear DNA indicated Neanderthals as a sister group of Denisovans after diverging from modern humans. However, the closer affinity of the Neanderthal mitochondrial DNA (mtDNA) to modern humans than Denisovans has recently been suggested as the result of gene flow from an African source into Neanderthals before 100,000 years ago.

The genetic history of Ice Age Europe.

Modern humans arrived in Europe ~45,000 years ago, but little is known about their genetic composition before the start of farming ~8,500 years ago. Here we analyse genome-wide data from 51 Eurasians from ~45,000-7,000 years ago. Over this time, the proportion of Neanderthal DNA decreased from 3-6% to around 2%, consistent with natural selection against Neanderthal variants in modern humans.

Pleistocene Mitochondrial Genomes Suggest a Single Major Dispersal of Non-Africans and a Late Glacial Population Turnover in Europe.

How modern humans dispersed into Eurasia and Australasia, including the number of separate expansions and their timings, is highly debated [1, 2]. Two categories of models are proposed for the dispersal of non-Africans: (1) single dispersal, i.e.

Studies on the biotransformation of the progestagen dienogest in the rabbit.

Following administration of 14 alpha, 15 alpha-3H-Dienogest (STS 557, 17 alpha-cyanomethyl-17 beta-hydroxy-4, 9-estradien-3-one) to female rabbits, extracts from urine, bile and plasma were separated by means of HPLC. Urinary and biliary metabolites are characterized by patterns of high complexity. From the mass spectra and UV absorption data of the urinary Dienogest metabolites a variety of biotransformation reactions has been derived like: hydroxylation in different positions of the Dienogest molecule, among these the 11-position; reduction of the 3-oxo group to 3-hydroxy; introduction of 2 and 4 hydrogen atoms; aromatization of ring A; transformation of 17 alpha-CH2CN to CH2OH, and formation of compounds with a 5(10), 9(11)-diene structure.

[Radioimmunoassay of the progestagen dienogest using various methods of sample preparation of plasma].

For the radioimmunological determination (RIA) of the progestagen dienogest (1, 17 alpha-Cyanomethyl-17 beta-hydroxy-estra-4,9-dien-3-one) in plasma three methods of sample preparation were tested and compared: Extraction of plasma samples with dichlormethane (I), binding of plasma dienogest to an antiserum added; removal of non-bound steroids by means of activated charcoal, extraction of dienogest using dichlormethane (II), using the RIA without extraction of plasma samples after partial precipitation of proteins by means of ammonium sulphate (III). The reliability of the dienogest-RIA is, characterized by a limit of detection of 3.2 pg (I, III) and 5 pg (II) per tube, respectively, by "within-assay"- and "between-assay" variation coefficients of 3 to 5% and 3 to 9%, respectively, in parallel determinations and by a high rate of recovery of dienogest (greater than 90%) added to plasma.

Studies on biotransformation of STS 557.

Transformation of STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) by female rat liver microsomes demonstrates a lower transformation rate in comparison with the analogous compound without 9-double bond: 17 alpha-cyanomethyl-19-nortestosterone, and the basic substance: 19-nortestosterone. 17 alpha-Cyanomethyl-estra-1, 3, 5(10), 9(11)-tetraene-3, 17 beta-diol, 17 alpha-cyanomethyl-11 beta, 17 beta-dihydroxy-estra-4, 9-dien-3-one, and tentatively 17 alpha-cyanomethyl-6 alpha, 17 beta-dihydroxy-estra-4, 9-dien-3-one were identified as metabolites. Microbial model investigations with species known to hydrogenate the 4-double bond in 4-en-3-oxo steroids stereospecifically to 5 alpha H- or 5 beta H-metabolites indicate 5 alpha-hydrogenation to be prevented in STS 557 by the 9-double bond, whereas 5 beta-hydrogenation is not affected.

Studies on pharmacokinetics of STS 557 in animal species and man.

Following oral and i.v. administration of [14 alpha, 15 alpha-3H]-STS 557 to beagle dogs, baboons, rats and female volunteers, plasma level courses of total radioactivity and STS 557, and radioactivity excretion in urine and feces have been investigated.

[Studies on the endocrine and spermatogenetic testicular function 6. In-vitro biosynthesis of testosterone in fractions of the smooth endoplasmic reticulum from the rat's testis in relationship to age and quality of dietary proteins].

The metabolic activity of testosterone biosynthesis in fractions of the unstriated endoplasmatic reticulum of testicular tissue in animals in puberty living on corn gluten was about 20 per cent below that in animals that were fed corn gluten plus supplemented amino acids. Such lowered metabolic activity was recordable even from adult animals for another 30 days despite change of feed to high-quality proteins. The conversion rate of progesterone in testostrone still was lowered by some ten per cent.