Phylogeographic Patterns in Africa and High Resolution Delineation of Genetic Clades in the Lion (Panthera leo).

Comparative phylogeography of African savannah mammals shows a congruent pattern in which populations in West/Central Africa are distinct from populations in East/Southern Africa. However, for the lion, all African populations are currently classified as a single subspecies (Panthera leo leo), while the only remaining population in Asia is considered to be distinct (Panthera leo persica). This distinction is disputed both by morphological and genetic data. In this study we introduce the lion as a model for African phylogeography. Analyses of mtDNA sequences reveal six supported clades and a strongly supported ancestral dichotomy with northern populations (West Africa, Central Africa, North Africa/Asia) on one branch, and southern populations (North East Africa, East/Southern Africa and South West Africa) on the other. We review taxonomies and phylogenies of other large savannah mammals, illustrating that similar clades are found in other species. The described phylogeographic pattern is considered in relation to large scale environmental changes in Africa over the past 300,000 years, attributable to climate. Refugial areas, predicted by climate envelope models, further confirm the observed pattern. We support the revision of current lion taxonomy, as recognition of a northern and a southern subspecies is more parsimonious with the evolutionary history of the lion.

Circannual variation in blood parasitism in a sub-Saharan migrant passerine bird, the garden warbler.

Knowing the natural dynamics of pathogens in migratory birds is important, for example, to understand the factors that influence the transport of pathogens to and their transmission in new geographical areas, whereas the transmission of other pathogens might be restricted to a specific area. We studied haemosporidian blood parasites of the genera Plasmodium, Haemoproteus and Leucocytozoon in a migratory bird, the garden warbler Sylvia borin. Birds were sampled in spring, summer and early autumn at breeding grounds in Sweden, on migration at Capri, Italy and on arrival and departure from wintering staging areas in West Africa: mapping recoveries of garden warblers ringed in Fennoscandia and Capri showed that these sites are most probably on the migratory flyway of garden warblers breeding at Kvismaren. Overall, haemosporidian prevalence was 39%, involving 24 different parasite lineages. Prevalence varied significantly over the migratory cycle, with relatively high prevalence of blood parasites in the population on breeding grounds and at the onset of autumn migration, followed by marked declines in prevalence during migration both on spring and autumn passage. Importantly, we found that when examining circannual variation in the different lineages, significantly different prevalence profiles emerged both between and within genera. Our results suggest that differences in prevalence profiles are the result of either different parasite transmission strategies or coevolution between the host and the various parasite lineages. When separating parasites into common vs. rare lineages, we found that two peaks in the prevalence of rare parasites occur; on arrival at Swedish breeding grounds, and after the wintering period in Africa. Our results stress the importance of appropriate taxonomic resolution when examining host-parasite interactions, as variation in prevalence both between and within parasite genera can show markedly different patterns.

Cross-species infection of blood parasites between resident and migratory songbirds in Africa.

We studied the phylogeny of avian haemosporidian parasites, Haemoproteus and Plasmodium, in a number of African resident and European migratory songbird species sampled during spring and autumn in northern Nigeria. The phylogeny of the parasites was constructed through sequencing part of their mitochondrial cytochrome b gene. We found eight parasite lineages, five Haemoproteus and three Plasmodium, infecting multiple host species. Thus, 44% of the 18 haemospiridian lineages found in this study were detected in more than one host species, indicating that host sharing is a more common feature than previously thought. Furthermore, one of the Plasmodium lineages infected species from different host families, Sylviidae and Ploceidae, expressing exceptionally large host range. We mapped transmission events, e.g. the occurrence of the parasite lineages in resident bird species in Europe or Africa, onto a phylogenetic tree. This yielded three clades, two Plasmodium and one Haemoproteus, in which transmission seems to occur solely in Africa. One Plasmodium clade showed European transmission, whereas the remaining two Haemoproteus clades contained mixes of lineages of African, European or unknown transmission. The mix of areas of transmission in several branches of the phylogenetic tree suggests that transmission of haemosporidian parasites to songbirds has arisen repeatedly in Africa and Europe. Blood parasites could be viewed as a cost of migration, as migratory species in several cases were infected with parasite lineages from African resident species. This cost of migration could have considerable impact on the evolution of migration and patterns of winter distribution in migrating birds.

Avian orientation at steep angles of inclination: experiments with migratory white-crowned sparrows at the magnetic North Pole.

The Earth's magnetic field and celestial cues provide animals with compass information during migration. Inherited magnetic compass courses are selected based on the angle of inclination, making it difficult to orient in the near vertical fields found at high geomagnetic latitudes. Orientation cage experiments were performed at different sites in high Arctic Canada with adult and young white-crowned sparrows (Zonotrichia leucophrys gambelii) in order to investigate birds' ability to use the Earth's magnetic field and celestial cues for orientation in naturally very steep magnetic fields at and close to the magnetic North Pole. Experiments were performed during the natural period of migration at night in the local geomagnetic field under natural clear skies and under simulated total overcast conditions. The experimental birds failed to select a meaningful magnetic compass course under overcast conditions at the magnetic North Pole, but could do so in geomagnetic fields deviating less than 3 degrees from the vertical. Migratory orientation was successful at all sites when celestial cues were available.

Orientation of snow buntings (Plectrophenax nivalis) close to the magnetic north pole

Orientation experiments were performed with first-year snow buntings (Plectrophenax nivalis) during their autumn migration in a natural near-vertical geomagnetic field approximately 400 km away from the magnetic north pole. Migratory orientation of snow buntings was recorded using two different techniques: orientation cage tests and free-flight release experiments. Experiments were performed under clear skies, as well as under natural and simulated complete overcast. Several experimental manipulations were performed including an artificial shift of the E-vector direction of polarized light, depolarization of incoming light and a 4 h slow clock-shift experiment. The amount of stored fat proved to be decisive for the directional selections of the buntings. Fat individuals generally chose southerly mean directions, whereas lean birds selected northerly headings. These directional selections seemed to be independent of experimental manipulations of the buntings' access to visual cues even in the local near-vertical magnetic field. Under clear skies, the buntings failed to respond to either a deflection of the E-vector direction of polarized light or an experimental depolarization of incoming skylight. When tested under natural as well as simulated overcast, the buntings were still able to select a meaningful mean direction according to their fat status. Similarly, the free-flight release test under complete overcast resulted in a well-defined southsoutheast direction, possibly influenced by the prevailing light northwest wind. Clock-shift experiments did not yield a conclusive result, but the failure of these birds to take off during the subsequent free-flight release test may indicate some unspecified confusion effect of the treatment.

Glioblastoma multiform in a dermoid cyst of the ovary.

Malignant transformation is reported in less than 2% of benign cystic teratomas. Although all the elements can undergo this transformation, it is most often seen in squamous epithelium. The malignancy of neural elements is probably the least common event, with only one case previously reported. A case of glioblastoma multiform in a benign cystic teratoma is presented. Its neural derivation was supported by an immunohistochemical staining specific for Glial Fibrillary Acidic Protein (GFAP). Despite very conservative surgery without adjuvant therapy, the patient remains alive and symptom free more than 3 years later.

Estrogen induction of liver proteins and high-density lipoprotein cholesterol: comparison between estradiol valerate and ethinyl estradiol.

The effects of ethinyl estradiol and estradiol valerate were compared in 135 postmenopausal women during estrogen replacement therapy. Subfractions of high-density lipoprotein (HDL) cholesterol and its apolipoproteins and the serum levels of 2 estrogen-sensitive liver proteins were followed during 3 cycles of unopposed treatment with either ethinyl estradiol 10 or 30 micrograms or estradiol valerate 2 mg daily. Estrogen therapy induced significant and dose-dependent changes in all serum factors except HDL3 cholesterol. The effects of 10 micrograms of ethinyl estradiol upon the lipoproteins were 1.5-2.5 times greater than those of 2 mg of estradiol valerate. Sex-hormone-binding globulin and the pregnancy zone protein were the most sensitive markers for the estrogenic effect and these 2 liver-derived plasma proteins were also much more sensitive to ethinyl estradiol than to estradiol valerate. Although satisfactory therapeutic effects were achieved with both estrogens, the marked influence of ethinyl estradiol on liver protein synthesis should make estradiol valerate the first choice in clinical replacement therapy.

Effects of progesterone, progestogens, and danazol on the specific cortisol binding in human plasma.

The interaction of medroxyprogesterone acetate (MPA) with cortisol binding to corticosteroid-binding globulin (CBG) was studied with the use of an aqueous two-phase system with polyethylene glycol and dextran for equilibrium partition. Competitive binding analyses were also performed for progesterone (P), levonorgestrel, norethisterone, danazol, and tamoxifen. P and danazol were found to exert cortisol displacing activity, whereas MPA and the other tested compounds had no such effect. The glucocorticoid effects reported for MPA could not be explained by displacement. In general, P serum concentrations are lower than those of cortisol, and most binding sites on CBG are occupied by the glucocorticoid. At high P levels displacement and an increase in free cortisol may occur. Danazol displacement of cortisol is hampered by its pronounced albumin binding. In conclusion, none of the tested compounds should increase free and biologically active cortisol during normal clinical treatment.

Subfractions of high-density lipoprotein cholesterol during estrogen replacement therapy: a comparison between progestogens and natural progesterone.

Subfractions of high-density lipoprotein cholesterol and its apolipoproteins were followed up in 58 postmenopausal women during three cycles of unopposed estrogen replacement therapy with 2 mg of estradiol valerate daily. During the last 10 days of the following three cycles the women received sequential addition of either 250 micrograms of levonorgestrel, 10 mg of medroxyprogesterone acetate, or 200 mg of natural micronized progesterone. Both progestogens significantly decreased total high-density lipoprotein cholesterol as well as subfraction 2 of high-density lipoprotein. Data suggest that doses and relative biologic activity of 19-norsteroids and 17-hydroxyprogesterone derivatives are more important for their metabolic effects than are qualitative differences. Natural progesterone had no apparent influence on high-density lipoprotein cholesterol or its subfractions and may develop into an attractive alternative to synthetic progestogens.

Oral progesterone and estrogen/progestogen therapy. Effects of natural and synthetic hormones on subfractions of HDL cholesterol and liver proteins.

The pharmacokinetics of progesterone after oral administration were investigated. After a single dose of 100 mg, serum concentrations of progesterone around 50-60 nM and of 20 alpha-hydroxy-4-pregnene-3-one around 5-6 nM were recorded within 1-4 hours and elevated levels persisted for 8-12 hours. There were only minor changes in 17 alpha-hydroxyprogesterone concentrations and serum levels of androstenedione and cortisol were unaffected. A significant conversion of circulating progesterone into deoxy-corticosterone was demonstrated. During clinical treatment with oral progesterone the individual serum concentrations of this potent mineralocorticoid were closely correlated to the progesterone concentrations. This observation could be important as regards the etiology of certain clinical disorders characterized by fluid retention. According to competitive binding analyses there was no evidence that progesterone or medroxyprogesterone acetate could cause significant displacement of cortisol from corticosteroid-binding globulin during clinical treatment. The effects of natural and synthetic hormones upon subfractions of high density lipoprotein (HDL) cholesterol and liver proteins were followed in postmenopausal women during replacement therapy with various estrogen-progestogen combinations. The total serum cholesterol level was significantly reduced during treatment with all estrogen regimens. The concentrations of HDL cholesterol, HDL2 cholesterol, apolipoprotein A I and A II were increased in a dose-dependent pattern during unopposed estrogen therapy. The potency of 10 micrograms of ethinyl estradiol was estimated to be equivalent to 3-4 mg of estradiol valerate. Estrogen effects were significantly reversed by levonorgestrel 250 micrograms and also by medroxyprogesterone acetate 10 mg. During treatment with natural progesterone, no changes were recorded in HDL cholesterol or its subfractions. As compared with the lipoproteins, pregnancy zone protein and sex hormone binding globulin (SHBG) were found to be more sensitive to the alkylated than to the non-alkylated estrogen. Both levonorgestrel and medroxyprogesterone acetate clearly reduced SHBG levels after 3 months, whereas micronized progesterone had no such effect. While tamoxifen counteracted the therapeutic and metabolic effects of estrogen the sequential addition of estriol had no apparent influence. Unopposed estrogen treatment enhanced liver lecithin synthesis along pathway I, i.e. reduced the amount of stearic acid and increased the amount of palmitic acid. The effects were dose-dependent and no qualitative differences between ethinyl estradiol and estradiol valerate were recorded.

Relative fatty acid composition of lecithin during postmenopausal replacement therapy--a comparison between ethinyl estradiol and estradiol valerate.

The relative fatty acid composition of serum lecithin was followed in groups of women during postmenopausal replacement therapy. The effects of estradiol valerate and ethinyl estradiol in two different doses, and the modulating influence of various progestogens and antiestrogens were compared. Unopposed estrogen treatment enhanced liver lecithin synthesis along pathway I, i.e. reduced the amount of stearic acid and increased the amount of palmitic acid. The effect was clearly dose-dependent and even the low dose of 10 micrograms of ethinyl estradiol was more potent than 2 mg of estradiol valerate. No qualitative difference between the two estrogens was recorded. The sequential addition of the antiestrogen tamoxifen significantly reduced the influence of ethinyl estradiol. Liver lecithin synthesis along pathway I may be stimulated by all estrogens and not only by 17C-alkylated compounds. The prostaglandin precursors, dihomogammalinolenic and arachidonic acid, showed a seemingly dose-dependent increase during estrogen treatment. The comparatively weaker effects of estradiol valerate on lipid metabolism should make this non-alkylated estrogen the first choice in clinical practice.

Effects of an antiestrogen on subfractions of HDL cholesterol during estrogen replacement therapy.

The antiestrogenic effects of tamoxifen and estriol were compared in 39 postmenopausal women during estrogen replacement therapy. Subfractions of HDL cholesterol and its apolipoproteins and the serum levels of two estrogen sensitive liver proteins were followed during three cycles of unopposed estrogen therapy with 10 micrograms ethinyl estradiol daily. During the last 10 days of the following three cycles the women received sequential addition of either 10 mg tamoxifen twice daily or 2 mg estriol twice daily. Tamoxifen clearly reduced the estrogen-induced increase of apolipoprotein AI, HDL2 cholesterol and total HDL cholesterol. In comparison the pregnancy zone protein and sex hormone-binding globulin were more sensitive to the estrogenic as well as to the antiestrogenic effect than the lipoproteins. Tamoxifen also counteracted the therapeutic effect on climacteric symptoms and it seems unlikely that this compound may be clinically useful as an alternative to progestogens during estrogen replacement therapy. The sequential addition of estriol had no apparent effects as compared to unopposed estrogen treatment.

Effects of sex hormone binding globulin capacity and pregnancy zone protein of treatment with combinations of ethinyl-oestradiol and norethisterone.

Sex hormone binding globulin (SHBG) and pregnancy zone protein (PZP) are two highly oestrogen-inducible serum proteins. SHBG capacity and PZP level were measured in 49 women treated with three different combinations of ethinyloestradiol and norethisterone. SHBG capacity and PZP were measured before and after 6 mth of treatment and both serum factors significantly increased during treatment for all three groups. PZP induction was found to be more sensitive and mainly to reflect the oestrogen component of a combined preparation while SHBG capacity was more sensitive to the modulating effect of the progestogen.